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Objective:To investigate the therapeutic effect of the combination of mouse nerve growth factor and edaravone in the treatment of carbon monoxide poisoning and its effect on patients′ cognitive function, lactic acid clearance rate, and related indicators of oxygen free radicals.Methods:A selection of 158 patients with carbon monoxide poisoning in the Huxi Hospital Affilliated Jining Medical College from May 2017 to June 2020 were divided into study group (80 cases) and control group (78 cases) according to the treatment plan. Both groups were given conventional treatment. On this basis, the control group was given edaravone, and the study group was given mouse nerve growth factor combined with edaravone, both of which were treated for 2 weeks. The clinical efficacy of the two groups was compared with those before treatment and 1 week and 2 weeks after treatment. Neurological impairment score (NIHSS), disease severity score (APACHE Ⅱ), cognitive function score (MMSE), serum inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP)], oxygen free radical related indicators [lipid peroxide (LPO), superoxide dismutase (SOD), gluten Glutathione peroxidase (GSH-PX), malondialdehyde (MDA)] levels, blood lactic acid levels before treatment and lactic acid clearance rates after 12 h, 24 h, 72 h treatment, and statistics of adverse reactions and 30-day mortality.Results:The total effective rate of the study group was higher than that of the control group after 2 weeks of treatment [95.00% (76/80) vs. 78.21% (61/78)] ( P<0.05); NIHSS and APACHEⅡ scores of the study group after 1 week and 2 weeks of treatment Lower than the control group: (6.08 ± 1.15) points vs. (8.94 ± 1.71) points, (4.58 ± 0.74) points vs. (6.32 ± 0.93) points and (6.79 ± 1.03) points vs. (8.02 ± 1.47) points, (5.94 ± 1.47) points vs. (7.25 ± 0.94) points, the MMSE score was higher than that of the control group: (22.09 ± 4.35) points vs. (19.34 ± 5.32) points, (26.05 ± 2.37) points vs. (22.47 ± 4.64) points ( P<0.05) After 1 and 2 weeks of treatment, the serum TNF-α, IL-6, CRP, LPO and MDA levels in the study group were lower than those in the control group: (22.62 ± 4.12) ng/L vs. (29.43 ± 4.68) ng/L and (18.21 ± 2.09) ng/L vs. (24.37 ± 3.16) ng/L, (39.67 ± 4.35) ng/L vs. (52.14 ± 5.48) ng/L and (34.83 ± 3.75) ng/L vs. (41.07 ± 4.09) ng/L, (12.63 ± 1.85) mg/L vs. (17.02 ± 2.47) mg/L and (8.27 ± 1.16) mg/L vs. (11.05 ± 1.62) mg/L, (11.06 ± 1.28) μmol/L vs. (15.97 ± 1.85) μmol/L and (8.24 ± 1.12) μmol/L vs. (12.97 ± 1.40) μmol/L, (7.15 ± 1.16) μmol/L vs. (9.02 ± 1.47) μmol/L and (6.12 ± 0.96) μmol/L vs. (7.84 ± 1.25) μmol/L, the levels of SOD and GSH-PX were higher than those in the control group ( P<0.05); the lactate clearance rate in the study group was higher than that in the control group after 12, 24 and 72 h of treatment: (18.49 ± 3.63)% vs. (14.62 ± 2.95)%, (23.19 ± 4.20)% vs. (17.42 ± 3.57)%, (29.86 ± 6.37)% vs. (25.38 ± 5.21)% ( P<0.05); the incidence of adverse reactions in the study group during treatment Compared with the control group, there was no significant difference ( P>0.05); there was no significant difference in the 30-day mortality between the study group and the control group ( P>0.05). Conclusions:The combination of mouse nerve growth factor and edaravone in the treatment of carbon monoxide poisoning can reduce the severity of disease and neurological deficits, improve cognitive function and lactate clearance rate, reduce inflammation and oxidative stress, improve efficacy, and have good safety.
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Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in the neonatal rats.Methods:Eighty SPF healthy newborn Sprague-Dawley rats of both sexes, aged 7 days, weighing 15-20 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), edaravone+ propofol group (group EP) and Nrf2 inhibitor ML385+ edaravone+ propofol group (group MEP). Propofol 75 mg/kg was intraperitoneally injected once a day for 7 consecutive days in P group, EP group and MEP group, respectively, while the equal volume of medium/long chain fat emulsion injection was intraperitoneally injected in C group. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before each propofol injection in EP and MEP groups, and ML385 15 mg/kg was intraperitoneally injected simultaneously in group MEP. The spontaneous activity was evaluated by the open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. The rats were sacrificed after the end of water maze test, and brains were removed and hippocampal tissues were obtained for determination of reactive oxygen species (ROS) levels (by flow cytometry), superoxide dismutase (SOD) and malondialdehyde (MDA) levels (by enzyme-linked immunosorbent assay) and expression of Nrf2 and HO-1 (by Western blot) and for microscopic examination of the pathological changes in the hippocampal CA1 area (using HE staining). Results:There was no significant difference in the speed, distance and time of stay at the center of the open field among the four groups ( P>0.05). Compared with C group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was observed in the hippocampal CA1 region in group P. Compared with P group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the levels of MDA and ROS in the hippocampus were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the pathological injury in the hippocampal CA1 region was significantly alleviated in EP group. Compared with EP group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was aggravated in the hippocampal CA1 region in MEP group. Conclusions:The mechanism by which edaravone attenuates long-term cognitive impairment caused by long-time sedation with propofol is related to activation of Nrf2/HO-1 signaling pathway and inhibition of oxidative stress in the neonatal rats.
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Objective:To evaluate the effect of edaravone on the extracellular signal-regulated kinase (ERK)-cAMP responsive element binding protein (CREB) signaling pathway in the hippocampus of aged rats with postoperative cognitive dysfunction (POCD).Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 650-700 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), POCD group (group P), edaravone group (group E) and ERK inhibitor group (group I). The rats received laparotomy under 3% sevoflurane anesthesia to prepare POCD model in P, E and I groups. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before operation in E and I groups, ERK inhibitor PD98059 0.3 mg/kg was injected via the tail vein in group I. The open field test was performed at 3 days after operation to evaluate the spontaneous activity of rats, then Morris water maze test was performed to evaluate the cognitive function of rats on 3-7 days after operation. The rats were sacrificed after the end of Morris water maze test, and hippocampal tissues were obtained for determination of the expression of phosphorylated ERK (p-ERK), phosphorylated CREB (p-CREB), synaptophysin and postsynaptic density protein 95 (PSD-95) (by Western blot) and dendrite length and density of dendrites in hippocampal CA1 area (using Golgi staining). Results:Compared with group C, the escape latency was significantly prolonged after operation, the number of crossing the original platform was reduced, the expression of p-ERK, p-CREB, synaptophysin and PSD-95 was down-regulated, and the dendritic length and density of hippocampal neurons were reduced in group P ( P<0.05). Compared with group P, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-ERK, p-CREB, synaptophysin and PSD-95 was up-regulated, and the dendritic length and density of hippocampal neurons were increased in group E ( P<0.05). Compared with group E, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-ERK, p-CREB, synaptophysin and PSD-95 was down-regulated, the dendritic length of hippocampal neurons was shortened, and the density of hippocampal neurons was decreased in group I( P<0.05). Conclusions:The mechanism by which edaravone improves POCD may be related to activating ERK/CREB signaling pathway and changing synaptic plasticity in hippocampal CA1 region in aged rats.
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Objective:To evaluate the role of phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase (Akt)/mammalian rapamycin target protein (mTOR) signaling pathway in edaravone-induced reduction of postoperative cognitive dysfunction in aged rats.Methods:Sixty healthy male Sprague-Dawley rats, aged 20 months, weighing 600-700 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), operation group (group O), edaravone group (group E) and PI3K inhibitor LY294002 group (group LY). The rats received laparotomy under 3% sevoflurane anesthesia in O, E and LY groups. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before operation in E and LY groups, and LY294002 0.3 mg/kg was simultaneously injected via the tail vein in group LY. Open field test was performed at 3 days after surgery to evaluate the spontaneous activity of rats, then Morris water maze test was performed to evaluate the cognitive function of rats. The rats were sacrificed after the end of behavioral experiment to isolate hippocampal tissues for determination of the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR), synaptophysin (SYP) and postsynaptic density protein 95 (PSD 95) (by Western blot ) and dendrite length in hippocampal CA1 area (using Golgi staining). The density of dendrites was calculated. Results:There were no statistically significant differences in exercise speed, distance, and time of staying at the center between the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, the dendritic length of neurons in hippocampal CA1 region was shortened, and the density of neurons in hippocampal CA1 region was decreased in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was up-regulated, the dendritic length of neurons in hippocampal CA1 region was prolonged, and the density of neurons in hippocampal CA1 region was increased in group E ( P<0.05). Compared with group E, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, and the dendritic length of neurons in hippocampal CA1 region was shortened, and the density of neurons in hippocampal CA1 region was decreased in group LY ( P<0.05). Conclusions:The mechanism by which edaravone reduces postoperative cognitive dysfunction is related to activating PI3K/Akt/mTOR signaling pathway and improving synaptic plasticity in aged rats.
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OBJECTIVE To evaluate efficacy， safety and cost-effectiveness of edaravone dexborneol and compound porcine cerebroside ganglioside in the treatment of acute ischemic stroke， and to provide decision-making reference for clinical treatment selection. METHODS The medical records of 488 patients with acute ischemic stroke hospitalized from Jan. 2021 to Dec. 2021 were collected and divided into two groups according to the treatment plan， i.e. 268 patients in edaravone dexborneol group， and 220 patients in compound porcine cerebroside ganglioside group. After baseline levels of the two groups were balanced using propensity score matching method， curative effect was evaluated according to the changes of NIHSS scores before and after treatment； the occurrence of adverse drug reactions in patients were collected from the hospital adverse reaction reporting system； from the perspective of China’s health system， the cost-effectiveness of the two options were analyzed， and one-way sensitivity analysis was conducted. RESULTS After the propensity score matching， 125 patients were included in the edaravone dexborneol group and compound porcine cerebroside ganglioside group， respectively. The response rates were 81.6% and 74.4%， respectively， with no significant difference. The average costs were 13 560.30 yuan and 14 958.68 yuan， respectively； the cost of edaravone dexborneol group was lower than that of compound porcine cerebroside ganglioside group. No adverse reaction reporting information was retrieved in both groups. Results of one-way sensitivity analysis showed that other drug costs in compound porcine cerebroside ganglioside group was relatively sensitive parameters. CONCLUSIONS Short-term efficacy and safety of edaravone dexborneol are equivalent to those of compound porcine cerebroside ganglioside in treating acute ischemic stroke. But edaravone dexborneol regimen had lower cost and is a more economical scheme.
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Objective:To evaluate the efficacy of Zhongfeng Xingnao liquid combined with conventional treatment for acute ischemic stroke (AIS).Methods:A total of 92 patients with AIS in our hospital from May 2020 to March 2021 who met the inclusion criteria were selected and divided into 2 groups according to the end number of the medical records, with 46 cases in each group. Both groups were given conventional western medicine therapy, and the control group added intravenous drip of edaravone injection, and the study group added Zhongfeng Xingnao liquid on the basis of the control group. Both groups were treated continuously for 2 weeks. Before and after treatment, the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) were used to evaluate the degree of neurological deficit and prognosis. The whole blood high-shear viscosity, hematocrit, whole blood low-shear viscosity, fibrinogen were detected by automatic blood rheometer, and the levels of high-sensitivity C-reactive protein (hs-CRP), IL-6 and endothelin-1 (ET-1) were detected by ELISA. Adverse events were recorded, and clinical effect rate was evaluated.Results:After treatment, the mRS score (2.06±0.18 vs. 2.73±0.23, t=15.56) and NIHSS score (5.25±2.36 vs. 10.61±2.48, t=14.58) of the study group were significantly lower than those in the control group ( P<0.01). The total clinical effective rate was 89.1% (41/46) in the study group and 69.6% (32/46) in the control group, with a statistically significant difference between the two groups ( χ2=5.37, P=0.020). After treatment, the serum levels of hs-CRP [(9.04±1.98)mg/L vs. (14.36±2.09)mg/L, t=12.57], IL-6 [(23.14±1.46)ng/L vs. (39.37±2.51)ng/L, t=12.39] and ET-1[(67.18±13.22)ng/L vs. (98.14±22.29)ng/L, t=19.37] in the study group were significantly lower than those in the control group ( P<0.01). The whole blood high shear viscosity [(7.53± 1.37)mPa·s vs. (9.24±1.42)mPa·s, t=5.89], hematocrit [(0.27±0.06)% vs. (0.39±0.08)%, t=8.14], whole blood low shear viscosity [(5.92±1.09)mPa·s vs. (8.35±1.24)mPa·s, t=9.98] and fibrinogen [(1.63±0.42) g/L vs. (2.47±0.58) g/L, t=7.96] were significantly lower than those in the control group ( P<0.01). During the treatment period, the incidence of adverse events was 8.70% (4/46) in the control group and 15.22% (7/46) in the study group, and there was no significant difference between the two groups ( χ2=0.93, P=0.335). After treatment, the good outcome rate was 73.9% (34/46) in the control group and 93.5% (43/46) in the study group, with a statistically significant difference between the two groups ( χ2=6.45, P=0.011). Conclusion:The Zhongfeng Xingnao liquid combined with edaravone injection can reduce the level of inflammatory cytokines in patients with AIS, improve hemorheological indicators, and play a role in brain protection.
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Objective:To observe the effect of edaravone dexborneol on anxiety and depression after stroke in rats, and to explore its possible mechanism.Methods:Totally 120 healthy adult male SD rats were randomly divided into sham operation group (sham), ischemia-reperfusion group (MCAO), edaravone group (Eda) and edaravone dexborneol group (ED) with 30 in each group.The middle cerebral artery occlusion (MCAO) model was established by thread occlusion.Rats in ED group and Eda group were intraperitoneally injected with edaravone(8 mg·kg -1·d -1) and edaravone dexborneol(edaravone: 8 mg·kg -1·d -1, dexborneol: 2 mg·kg -1·d -1) respectively.And rats in the other two groups were intraperitoneally injected with the same volume of normal saline.Some rats were killed after continuous administration for 3 days to detect molecular indexes, and the remaining rats were tested for behavior after continuous administration for 14 days.The levels of neclear factor κB(NF-κB)、phosphorylated NF-κB(p-NF-κB)、tumor necrosis α(TNF-α)、interleukin 1β(IL-1β) were detected by Western blot.The mRNA levels of TNF-α, IL-1β, cluster of differentiation 86(CD86), cluster of differentiation 206(CD206), inducible nitric oxide synthase(iNOS) were detected by RT-qPCR.M1 type microglia labeled with CD68, microglia labeled with ionized calcium binding adaptor molecule 1(Iba1) and neurons labeled with microtubule-associated protein 2(MAP2) were detected by immunofluorescence staining.The cerebral infarction volume was measured by TTC staining.Depression and anxiety behavior after stroke in rats was observed by the open field test and elevated plus maze test.SPSS 17.0 software was used for statistical analysis of the data.One-way ANOVA was used for multiple group comparison, and LSD-t test was used for pairwise comparison. Results:(1) The behavioral results showed that 14 days after ischemia-reperfusion, the number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the open field in the MCAO group were lower than those in the sham group ( t=20.77, 6.02, 14.63, all P<0.05). The number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the field in the ED group ( (16.22±0.49) times, (69.11±17.08) s, (3.80±0.37) s) were higher than those in the MCAO group ( (8.14±0.60) times, (41.18±9.81) s, (0.33±0.39) s) ( t=4.69, 0.38, 2.27, all P<0.05) and Eda group ( (11.11±0.26) times, (45.26±17.16) s, (1.14±0.19) s) ( t=8.63, 2.50, 7.86, all P<0.05). (2) Western blot results showed that 3 days after ischemia-reperfusion, p-NF-κB/NF-κB, TNF-α, and IL-1β levels in the MCAO group were higher than those in the sham group ( t=15.35, 12.35, 7.23, all P<0.05). The levels of p-NF-κB/NF-κB (0.49±0.02), TNF-α (0.73±0.03), IL-1β (0.61±0.01) of ischemic penumbra cortex in ED group were significantly lower than those of the MCAO group ( (1.14±0.05), (1.13±0.07), (1.34±0.14)) ( t=14.58, 7.86, 5.65, all P<0.05) and Eda group ( (0.93±0.03), (0.89±0.02), (1.04±0.36) ) ( t=9.82, 3.07, 3.30, all P<0.05). (3) RT-qPCR results showed that the level of TNF-α mRNA (1.98±0.18), IL-1β mRNA (2.00±0.35), CD86 mRNA (1.56±0.20) and iNOS mRNA (2.01±0.12) in the peri-infarct cortex of ED group were lower than those in the MCAO group ( (5.12±0.24), ( 8.15±0.22), (6.03±0.13), (7.20±0.09) ) ( t=7.86, 16.88, 16.55, 37.25, all P<0.05) and Eda group ( (2.85±0.07), (5.43±0.26), (2.67±0.27), (3.58±0.11) ) ( t=3.71, 9.41, 4.13, 11.30, all P<0.05). The level of CD206 mRNA in the peri-infarct cortex of the ED group (3.98±0.25) was higher than that in the MCAO group (2.00±0.11) ( t=7.08, P<0.05) and Eda group (3.17±0.09) ( t=3.25, P<0.05). (4) The results of immunofluorescence staining showed that the ratio of polarized M1 microglia in the peri-infarct cortex and striatum in the ED group ((20.36±9.23)%, (18.26±5.98)%)were lower than those in the MCAO group ( (83.69±12.79)%, (61.25±33.26)%) ( t=5.23, 3.02, both P<0.05) and Eda group((42.16±13.13)%, (40.23±14.22)%)( t=3.12, 2.08, both P<0.05). In addition, the number of neurons marked with MAP2 of peri-infarct cortex in the MCAO group was lower than that in the sham group( t=8.02, P<0.05), and the number of neurons marded with MAP2 of peri-infarct cortex in the ED group ((53.07±17.90) /scope) was higher than that in the MCAO group ( (26.27±9.95) /scope) ( t=6.89, P<0.05) and Eda group ( (38.69±12.03)/scope) ( t=5.26, P<0.05). (5) The results of TTC staining showed that the cerebral infarction volume in ED group ( (10.31±1.03)%) was lower than that in the MCAO group ( (34.71±1.74)%) ( t=15.31, P<0.05) and Eda group ( (26.05±1.00)%) ( t=9.88, P<0.05). Conclusion:Edaravone dexborneol can alleviate anxiety and depression in rats with cerebral ischemia-reperfusion, which may be related to the inhibition of M1 microglial polarization, the down-regulation of NF-κB signaling pathway and the enhancement of neuronal structural stability.
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OBJECTIVES: To investigate the molecular mechanism of edaravone (EDA) in improving the post-traumatic brain injury (TBI) dysfunction in learning and memory. METHODS: In vitro and in vivo TBI models were established using hydrogen peroxide (H2O2) treatment for hippocampal nerve stem cells (NSCs) and surgery for rats, followed by EDA treatment. WST 1 measurement, methylthiazol tetrazolium assay, and flow cytometry were performed to determine the activity, proliferation, and apoptosis of NSCs, and malondialdehyde (MDA), lactic dehydrogenase (LDH), and reactive oxygen species (ROS) detection kits were used to analyze the oxides in NSCs. RESULTS: Following EDA pretreatment, NSCs presented with promising resistance to H2O2-induced oxidative stress, whereas NSCs manifested significant increases in activity and proliferation and a decrease in apoptosis. Meanwhile, for NSCs, EDA pretreatment reduced the levels of MDA, LDH, and ROS, with a significant upregulation of Nrf2/antioxidant response element (ARE) signaling pathway, whereas for EDA-treated TBI rats, a significant reduction was observed in the trauma area and injury to the hippocampus, with improvement in memory and learning performance and upregulation of Nrf2/ARE signaling pathway. CONCLUSIONS: EDA, by regulating the activity of Nrf2/ARE signal pathway, can improve the TBI-induced injury to NSCs and learning and memory dysfunction in rats.
Subject(s)
Animals , Rats , Antioxidant Response Elements , Brain Injuries, Traumatic/physiopathology , Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/drug therapy , Edaravone/pharmacology , Learning/drug effects , Signal Transduction/drug effects , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , Oxidative Stress/drug effects , NF-E2-Related Factor 2/metabolism , Memory/drug effectsABSTRACT
Objective:To evaluate the effect of edaravone on mitochondrial function during ketamine-induced apoptosis in PC12 cells.Methods:Nerve growth factor (NGF)-induced differentiating PC-12 cells were divided into 3 groups ( n=30 each) using a random number table method: control group (group C), ketamine group (group K) and edaravone plus ketamine group (group EK). Cells in group C were commonly cultured.In group K, PC12 cells were incubated with PBS and 100 μmol/L ketamine at 7 days after differentiation.In group EK, cells were incubated with 10 μmol/L edaravone and 100 μmol/L ketamine.The cell viability, caspase-3/7 activity, reactive oxygen species (ROS) activity, adenosine triphosphate (ATP) content and NADH/NAD + ratio were determined using analysis kits at 24 h of incubation.The cell apoptosis was observed by TUNEL assay and apoptosis rate was calculated. Results:Compared with group C, the cell viability, caspase-3/7 activity, NADH/NAD + ratio and apoptosis rate were significantly increased, and ROS activity and ATP content were decreased in group K ( P<0.05). Compared with group K, the cell viability, caspase-3/7 activity, NADH/NAD + ratio and apoptosis rate were significantly decreased, and ROS activity and ATP content were increased in group EK ( P<0.05). Conclusion:The mechanism by which edaravone inhibits ketamine-induced apoptosis in PC12 cells is related to improving mitochondrial function.
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Objective:To investigate the effect of edaravone, a free radical scavenger, on the regulation of retinal autophagy and the protection of photoreceptor cells at the early stage of experimental retinal detachment (RD) in rats.Methods:Fifty-one adult male Sprague-Dawley rats were used for RD model establishment, and another 24 rats were served as PBS injection group.The RD model was established via subretinal injection of 0.5% sodium hyaluronate into the right eye of the rats and the rats with successful modeling were randomly divided into RD model group and edaravone treatment group.The rats in the edaravone treatment group were given edaravone of 3 mg/kg intraperitoneally, twice a day after modeling, and the rats in the PBS injection group and RD model group were given equal volume of normal saline.Rats were sacrificed on the 1st day, 3rd day and 7th day following modeling.The T-superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) content in the intraocular fluid was detected.The expression levels of superoxide dismutase 2 (SOD2), nuclear factor E2-related factor 2 (Nrf2), autophagy related gene 4 (Atg4), microtubule-associated protein 1 light chain 3B (LC3B) and other proteins in retinal tissue were identified by Western blot analysis.TUNEL staining was performed on paraffin sections of the whole eyeball to analyze the apoptosis of photoreceptor cells.The study protocol was approved by an Ethics Committee of Xi'an Fourth Hospital (No. 2016016). The use and care of animals complied with the Regulations on the Administration of Experimental Animals.Results:The RD area was more than 60% in rat eyes of RD model.There were significant differences in MDA content and T-SOD activity among different groups at various time points (MDA: Fgroup=385.513, P<0.01; Ftime=13.021, P<0.01.T-SOD: Fgroup=48.865, P<0.01; Ftime=7.700, P=0.003). Compared with the PBS injection group, the MDA concentration was significantly increased and the T-SOD activity was significantly decreased in the RD group and edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05). The MDA concentration was significantly reduced and the T-SOD activity was significantly elevated in the edaravone treatment group on the 1st, 3rd and 7th day after modeling in comparison with those of the RD group (all at P<0.05). Compared with the PBS injection group, the relative expression levels of SOD2 and Nrf2 proteins were significantly increased in the RD group and edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased on the 1st, 3rd and 7th day after modeling (all at P<0.05). The expression level of SOD2 in the edaravone treatment group was significantly higher than that in the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and the expression level of Nrf2 was significantly increased in the edaravone treatment group on the 1st and 3rd day after modeling compared with that of the RD group (both at P<0.05), and the expression levels of Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased in the edaravone treatment group on the 3rd day after modeling in comparison with those of the RD group (both at P<0.05). No significant TUNEL positive cells were observed in PBS injection group at all time points, and TUNEL positive cells were observed on the 1st, 3rd and 7th day after modeling in the RD group, and the expression level of caspase-3 in the RD group was significantly increased in comparison with that of the PBS injection group ( P<0.05). The apoptosis of photoreceptor cells and the expression level of caspase-3 in edaravone treatment group were significantly decreased in comparison with those of the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05). Conclusions:The intraperitoneal injection of edaravone, twice a day, can significantly improve the antioxidant capacity of the retina after experimental RD in rats, regulate retinal autophagy and reduce the apoptosis of photoreceptor cells in early-stage RD.
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OBJECTIVE：To compare the protective effect of atomization inhalation and intraperitoneal injection of edaravone on acute lung injury in smoke inhalation lung injury model rats. METHODS ：Thirty male SD rats were divided into normal control group（group A ），injury group （group B ），intraperitoneal injection group （group C ），low-dose aerosol inhalation group （group D），high-dose aerosol inhalation group （group E ）according to random numble table ，with 6 rats in each group. Group B-E were placed in smoke generator containing pine sawdust to induce smoke inhalation lung injury model. In group A ，the operation was the same as above except that the pine sawdust was not placed. Thirty minutes after modeling ，group C were injected intraperitoneally with edaravone 18 mg/kg（every 70 min，4 times in total ）. Group D and E inhaled edaravone 9，1.8 mg/kg（every 60 min，lasting for 10 min each time ，4 times in total ）. The rats were treated by no means in group A and group B. Six hours after last medication，arterial blood gas analysis was performed ，and the lung wet to dry ratio （W/D）and water content of lung tissue were calculated. The levels of TNF-α，IL-6 and IL- 10 in serum were detected by double antibody ELISA. The contents of MDA ，MPO， SOD and Caspase- 3 in lung tissue were determined by ELISA and other methods. HE staining was used to observe the pathological changes of lung tissue. The apoptotic rate of cells in lung tissue were determined by TUNEL assay. RESULTS ：No abnormality was found in lung tissue of group A ；in group B ，hemorrhage and edema were found in lung tissue ，alveolar structure was difficult to identify，and inflammatory cells and red blood cell infiltration were seen. Above symptoms of rats in group C-E were improved to different extent. Compared with group A ，PaO2/FiO2 and SOD content of lung tissue were decreased significantly in other groups （P＜0.05）；water content of lung tissue ，W/D，serum contents of TNF-α，IL-6 and IL- 10，the contents of MDA ，MPO and Caspase-3 in lung tissue ，apoptotic rate were increased significantly （P＜0.05）. Compared with group B ，PaO2/FiO2 and serum contents of IL- 10 were increased significantly in administration groups （P＜0.05）；water content of lung tissue ，W/D，serum contents of TNF-α and IL-6，the contents of MDA ，MPO and Caspase- 3 in lung tissue ，apoptotic rate were significantly decreased，in dose-dependent manner （P＜0.05）. CONCLUSIONS ：Edaravone has a certain protective effect on smoke inhalation lung injury model rat. It can reduce the production and release of inflammatory mediators and/or cytokines ，reduce the peroxide damage and inhibit cell apoptosis in a dose-dependent manner. The effect of atomization inhalation is more obvious than that of intraperitoneal injection.
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BACKGROUND: Kidney ischemia-reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. This study aimed to identify whether EDA improved kidney function in rats with ischemia-reperfusion injury by regulating the JAK/STAT pathway and clarify the underlying mechanism. METHODS: Histomorphological analysis was used to assess pathological kidney injury, and mitochondrial damage was observed by transmission electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) staining was performed to detect tubular epithelial cell apoptosis. The expression of JAK2, P-JAK2, STAT3, P-STAT3, STAT1, P-STAT1, BAX and Bcl-2 was assessed by western blotting. Mitochondrial function in the kidney was assessed by mitochondrial membrane potential (ΔψM) measurement. RESULTS: The results showed that EDA inhibited the expression of p-JAK2, p-STAT3 and p-STAT1, accompanied by downregulation of the expression of Bax and caspase-3, and significantly ameliorated kidney damage caused by ischemia-reperfusion injury (IRI). Furthermore, the JC-1 dye assay showed that edaravone attenuated ischemia-reperfusion-induced loss of kidney (ΔψM). CONCLUSION: Our findings indicate that EDA protects against kidney damage caused by ischemia-reperfusion through JAK/STAT signaling, inhibiting apoptosis and improving mitochondrial injury.
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Animals , Male , Rats , Reperfusion Injury/drug therapy , Free Radical Scavengers/pharmacology , Edaravone/pharmacology , Signal Transduction/drug effects , Rats, Sprague-Dawley , Apoptosis , STAT Transcription Factors/drug effects , Janus Kinases/drug effects , MitochondriaABSTRACT
Objective To investigate the effect of Danhong injection combined with edaravone in the treatment of patients with acute cerebral infarction,and its influence on cytokines,cerebral hemodynamics and vascular endothelial function.Methods From March 2018 to March 2019,142 patients with acute cerebral infarction treated in the People's Hospital of Yuhuan were randomly divided into treatment group and control group according to the digital table,with 71 cases in each group.The treatment group was treated with Danhong injection combined with edaravone,while the control group was only treated with edaravone.Both two groups were treated for 2 weeks.The therapeutic effects,changes of cytokines,cerebral hemodynamics,vascular endothelial function,activity of daily living index(Barthel index) and neurological deficit score(NIHSS score) before and after treatment were compared between the two groups.Results The total effective rate of the treatment group was 90.14％ (64/71),which was higher than 74.65％ (53/71) of the control group,the difference was statistically significant(x2 =5.874,P ＜ 0.05).After treatment,the serum levels of CRP [(5.43 ± 1.20) mg/L] and IL-6 [(32.15 ± 7.39) ng/L] in the treatment group were lower than those in the control group [(9.38 ± 1.74) mg/L and (67.43 ± 10.29) ng/L] (t =15.747,23.465,all P ＜0.05).After treatment,the Vp [(69.83 ± 3.24) v ·-1 · s-1] and Vm [(35.24 ± 2.10) v ·-1 · s-1] in the treatment group were higher than those in the control group [(63.81 ± 2.68) v ·-1 · s-1 and (32.18 ± 1.73) v ·-1s-1],while the PI in the treatment group [(0.72 ± 0.04)] was lower than that in the control group [(0.83 ±0.07)],the differences were statistically significant (t =12.064,9.477,11.497,all P ＜ 0.05).After treatment,the serum level of ET-1 [(60.17 ± 5.46) mg/L] in the treatment group was lower than that in the control group[(73.21 ±6.78)mg/L],while the NO level in the treatment group[(72.15 ±7.39) ng/L] was higher than that in the control group [(61.43 ± 10.29) ng/L],the differences were statistically significant (t =12.622,7.130,all P ＜0.05).After treatment,the Barthel index score of the treatment group [(68.93 ± 7.83) points] was higher than that of the control group [(54.57 ± 7.38)points],while the NIHSS score of the treatment group [(9.34 ± 1.97)points] was lower than that of the control group [(14.54 ± 2.89) points],the differences were statistically significant (t =11.246,12.528,all P ＜ 0.05).Conclusion Danhong injection combined with edaravone in the treatment of acute cerebral infarction is effective,which can alleviate inflammation and improve cerebral hemodynamics and vascular endothelial dysfunction.
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Objective To observe the effect of edaravone (EDA) on the expressions of malondialdehyde (MDA), phosphorylated extracellular signal-regulated kinase (p-ERK), nuclear factor kappa-B cells (NF-κB) and Collagen-III in rat model of unilateral ureteral obstruction (UUO), and discuss the protective effect of EDA on renal-interstitial fibrosis. Methods Fifty-four male SD rats were randomly divided into three groups (18 each): sham group (normal control), UUO group and EDA group. Rats in UUO group and EDA group received UUO operation. One day before UUO operation, rats in EDA group received intraperitoneal injection of 3.75mg/(kg·d) EDA, and those in sham group and UUO group were injected with equivalent normal saline. Rats were sacrificed in three batches at the 3rd, 7th and 14th day after operation, six from each group in each batch. The renal pathological changes were observed via HE staining and Masson staining. The contents of MDA in renal tissues were determined by spectrophotometry, and the expression levels of p-ERK1/2, NF-κB and collagen-III were detected by immunohistochemistry. Results HE and Masson staining showed no significant changes of MDA content, renal tubules and interstitium in sham group at 3rd, 7th and 14th day, but obvious changes of interstitium and increased fibre deposition in UUO group and EDA group compared with sham group. Compared with UUO group, the lesions of renal tubular and interstitium significantly reduced and the interstitial fibrosis deposition decreased in EDA group. Spectrophotometry indicated that the MDA contents showed no significant difference between EDA group and UUO group [(9.261±0.496)nmol/mg prot and (10.143±0.301)nmol/mg prot] on the 3rd day after operation, but was higher than in sham group [(6.918±1.120)nmol/mg prot]. The MDA contents at the 7th and 14th day after surgery in EDA group [(11.545±0.620)nmol/mg prot and (15.203±0.512)nmol/mg prot] were significantly lower than in UUO group [(13.405±0.612)nmol/mg prot and (18.133±1.684)nmol/mg prot]. Immunohistochemistry analysis showed that no significant difference existed in the expressions of p-ERK1/2, NF-κB and Collagen III at the 3 time points in sham group; At the 3rd day after surgery, the expressions of p-ERK1/2, NF-κB and Collagen III were higher in EDA group (19 055.7±1866.1, 11 217.0±989.9 and 9724.1±341.9) than in sham group (14 100.3±1822.7, 7975.1±2058.5 and 6890.0±2389.9, P0.05). At the 7th and 14th day after surgery, the expression level of p-ERK1/2 was significantly lower in EDA group (26 228.0±523.0 and 30 647.1±583.8) than in UUO group (28 254.9±886.6 and 33 240.3±1330.4); the expression level of NF-κB was obviously lower in EDA group (16 374.4±1045.3 and 21 111.2±1022.5) than in UUO group (18 799.4±357.0 and 27 125.2±2873.3); the expression level of Collagen-III was markedly lower in EDA group (12 470.9±506.1 and 19 615.8±1120.1) than in UUO group (15 049.9±1372.3 and 22 868.9±1889.2), all the differences were of statistical significance (P<0.05). Conclusion Oxidative stress and the signaling pathway of p-ERK1/2 and NF-κB may play a role in the progress of renal interstitial fibrosis (RIF) in UUO rat model, and EDA may have an antifibrosis effect by down-regulating the levels of oxidative stress in kidney tissue and inhibiting the signaling pathway of p-ERK1/2 and NF-κB.
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Objective@#To explore the treatment effects of edaravone combined with antiviral drugs on 30 adult cases with viral encephalitis.@*Methods@#Sixty adult patients with viral encephalitis in our hospital were selected for the study and were divided into control group and observation group according to the admission number, with 30 cases in each group. Control group was treated with conventional antiviral drugs, and observation group was given antiviral drugs combined with edaravone. Another 30 healthy people admitted to the hospital in the same period for physical examination were included in healthy group. The clinical efficacy and time to normalization of clinical manifestations (fever, headache, vomiting, EEG abnormalities) were recorded in observation group and control group, and the oxidative stress indicators [catalase (CAT), lipids peroxide (LPO)] and nerve injury indexes [neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP)] were compared between observation group, control group and healthy group before treatment and after 2 weeks of treatment. The neurological deficit [National Institutes of Health Stroke Scale (NIHSS)] was observed in observation group and control group.@*Results@#The clinical efficacy in observation group was significantly better than that in control group (P<0.05), and the normal recovery times of fever, headache, vomiting and abnormal EEG were lower than those in control group (P<0.05). After 2 weeks of treatment, the partial oxidative stress index (serum CAT) in observation group and control group was higher than that before treatment (P<0.05) while partial oxidative stress index (serum LPO), nerve injury indexes (serum NSE, GFAP) and neurological defect (NIHSS score) were lower than those before treatment (P<0.05), and the changes in observation group were greater than those in control group (P<0.05). The serum CAT levels in the two groups before and after treatment were lower than those in healthy group (P<0.05), and the levels of LPO, NSE and GFAP were higher than those in healthy group (P<0.05).@*Conclusions@#Edaravone combined with antiviral drugs has significant treatment effects in the treatment of adult viral encephalitis. It can not only reduce the body’ s oxidative stress response, but also reduce nerve injury and improve neurological deficit, and it has a certain application value.
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Objective@#To investigate the effects of Shuxuening injection combined with edaravone on neurological function, serum vascular endothelial growth factor (VEGF) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with cerebral infarction.@*Methods@#A total of 112 patients with cerebral infarction admitted to Zhejiang Provincial Armed Police Hospital from August 2016 to August 2018 were enrolled in the study.They were divided into observation group and control group according to the digital table, with 56 patients in each group.The two groups were given routine symptomatic treatment.On the basis of this, the control group was given edaravone treatment, and the observation group was given Shuxuening injection combined with edaravone.The changes of NIHSS, GCS score, serum NSE, NGF, NTF, VEGF and sVCAM-1 levels before and after treatment were compared between the two groups, and the clinical efficacy was compared.@*Results@#After treatment, the effective rate of the observation group was 92.86%(52/56), which was higher than that of the control group 73.21%(41/56), the difference was statistically significant (χ2=7.669, P<0.05). After treatment, the NIHSS score, NSE, sVCAM-1 of the two groups were decreased, which of the observation group were lower than those of the control group[(3.27±1.16)points vs.(6.32±2.12)points, (13.15±1.14)μg/L vs.(17.64±1.89)μg/L, (648.56±134.67)ng/mL vs.(1 078.36±131.23)ng/mL], while the GCS score, NGF, NTF, VEGF levels of the two groups were elevated, which of the observation group were higher than those of the control group[(13.64±3.86)points vs.(11.89±3.41)points, (76.13±8.72)μg/L vs.(68.24±7.25)μg/L, (5.14±0.36)μg/L vs.(3.74±0.29)μg/L, (831.51±91.67)ng/L vs.(752.83±91.24)ng/L], the differences were statistically significant (t=9.414, 2.543, 15.223, 5.205, 22.663, 4.552, 15.672, all P<0.05).@*Conclusion@#Shuxuening injection combined with edaravone can improve the curative effect of patients with cerebral infarction, improve neurological function, effectively improve serum VEGF level and decrease sVCAM-1 level.It is worthy of clinical application.
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Objective@#To investigate the effects of butylphthalide combined with edaravone on cerebral hemodynamics, vascular endothelial function and cytokines in elderly patients with acute cerebral infarction.@*Methods@#From May 2017 to May 2018, 82 elderly patients with acute cerebral infarction admitted to the First People's Hospital of Wenling were selected and randomly divided into two groups according to the digital table, with 41 cases in each group.The patients in the control group were treated with edaravone, while the patients in the treatment group were treated with butylphthalide on the basis of the control group.The two groups were treated for 2 weeks.The neurological deficit scale (NIHSS), cerebral hemodynamics, vascular endothelial function and cytokines were compared between the two groups before and after treatment.@*Results@#The NIHSS score of the treatment group was (18.49±1.87)points, which was lower than (22.17±1.32)points of the control group at 2 weeks after treatment (t=10.294, P<0.05). The mean flow velocity [(31.70±3.25)cm/s], vascular resistance index (0.79±0.12) and maximum peak flow velocity [(54.21±2.65)cm/s] in the treatment group were higher than those in the control group [(26.91±4.39)cm/s, (0.61±0.05) and (43.76±3.10)cm/s] (t=5.615, 8.866, 16.407, all P<0.05). The contents of NO [(71.27±6.58)μmol/L] and eNOS [(66.37±3.65)U/mL] in the treatment group were higher than those in the control group [(62.30±2.71)μmol/L and (57.89±4.08)U/mL] (t=8.071, 9.919, all P<0.05). After 2 weeks of treatment, the contents of IL-6 [(27.36±2.71)pg/mL], CRP [(2.87±0.76)mg/L] and TNF- α[(98.24±10.48)ng/mL] in the treatment group were lower than those in the control group [(43.25±4.10)pg/mL, (4.59±0.91)mg/L and (160.27±15.42)ng/mL] (t=20.702, 9.289, 21.303, all P<0.05). The total effective rate of treatment group (90.24%) was higher than that of control group (68.29%) (χ2=6.011, P<0.05).@*Conclusion@#Butylphthalide combined with edaravone can improve cerebral hemodynamics, vascular endothelial function and alleviate cellular inflammatory reaction in elderly patients with acute cerebral infarction, and the curative effect is significant, which is worthy of clinical study.
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To investigate the effects of Shuxuening injection combined with edaravone on neuro -logical function,serum vascular endothelial growth factor ( VEGF) and soluble vascular cell adhesion molecule -1 (sVCAM-1) in patients with cerebral infarction.Methods A total of 112 patients with cerebral infarction admitted to Zhejiang Provincial Armed Police Hospital from August 2016 to August 2018 were enrolled in the study.They were divided into observation group and control group according to the digital table ,with 56 patients in each group.The two groups were given routine symptomatic treatment.On the basis of this, the control group was given edaravone treatment,and the observation group was given Shuxuening injection combined with edaravone .The changes of NIHSS, GCS score,serum NSE,NGF,NTF,VEGF and sVCAM -1 levels before and after treatment were compared between the two groups,and the clinical efficacy was compared.Results After treatment,the effective rate of the observation group was 92.86%(52／56),which was higher than that of the control group 73.21%(41／56),the difference was statistically significant (χ2 ＝7.669,P＜0.05).After treatment,the NIHSS score,NSE,sVCAM-1 of the two groups were decreased,which of the observation group were lower than those of the control group [(3.27 ±1.16)points vs. (6.32 ±2.12)points,(13.15 ±1.14)μg／L vs.(17.64 ±1.89)μg／L,(648.56 ±134.67)ng／mL vs.(1 078.36 ± 131.23 ) ng／mL], while the GCS score, NGF, NTF, VEGF levels of the two groups were elevated , which of the observation group were higher than those of the control group [(13.64 ±3.86) points vs.(11.89 ±3.41) points, (76.13 ±8.72) μg／L vs.( 68.24 ±7.25 ) μg／L, ( 5.14 ±0.36 ) μg／L vs.(3.74 ±0.29) μg／L, (831.51 ± 91.67)ng／L vs.(752.83 ±91.24) ng／L],the differences were statistically significant (t＝9.414,2.543,15.223, 5.205,22.663,4.552,15.672,all P ＜0.05).Conclusion Shuxuening injection combined with edaravone can improve the curative effect of patients with cerebral infarction ,improve neurological function,effectively improve serum VEGF level and decrease sVCAM -1 level.It is worthy of clinical application.
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Objective To investigate the effects of butylphthalide combined with edaravone on cerebral hemodynamics,vascular endothelial function and cytokines in elderly patients with acute cerebral infarction.Methods From May 2017 to May 2018,82 elderly patients with acute cerebral infarction admitted to the First People's Hospital of Wenling were selected and randomly divided into two groups according to the digital table,with 41 cases in each group.The patients in the control group were treated with edaravone,while the patients in the treatment group were treated with butylphthalide on the basis of the control group.The two groups were treated for 2 weeks.The neurological deficit scale (NIHSS),cerebral hemodynamics,vascular endothelial function and cytokines were compared between the two groups before and after treatment.Results The NIHSS score of the treatment group was (18.49 ±1.87)points,which was lower than (22.17 ± 1.32)points of the control group at 2 weeks after treatment (t =10.294,P＜0.05).The mean flow velocity [(31.70 ±3.25)cm/s],vascular resistance index (0.79 ±0.12) and maximum peak flow velocity [(54.21 ± 2.65)cm/s] in the treatment group were higher than those in the control group [(26.91 ± 4.39) cm/s,(0.61 ± 0.05) and (43.76 ± 3.10) cm/s] (t =5.615,8.866,16.407,all P ＜0.05).The contents of NO [(71.27 ± 6.58) μmol/L] and eNOS [(66.37 ± 3.65) U/mL] in the treatment group were higher than those in the control group [(62.30 ±2.71) μmol/L and (57.89 ±4.08) U/mL] (t =8.071,9.919,all P ＜ 0.05).After 2 weeks of treatment,the contents of IL-6 [(27.36 ± 2.71) pg/mL],CRP [(2.87 ±0.76) mg/L] and TNF-α[(98.24 ± 10.48) ng/mL] in the treatment group were lower than those in the control group [(43.25 ±4.10) pg/mL,(4.59 ±0.91) mg/L and (160.27 ± 15.42) ng/mL] (t =20.702,9.289,21.303,all P ＜ 0.05).The total effective rate of treatment group (90.24％) was higher than that of control group (68.29％)(x2 =6.011,P ＜ 0.05).Conclusion Butylphthalide combined with edaravone can improve cerebral hemodynamics,vascular endothelial function and alleviate cellular inflammatory reaction in elderly patients with acute cerebral infarction,and the curative effect is significant,which is worthy of clinical study.
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Objective To observe the influence of edaravin combined with cerebroside-kinin on the level of glial fiber acidic protein (GFAP) and ubiquitin carboxyl terminal-L1 (UCH-L1) in the treatment of severe craniocerebral injury.Methods From January 2016 to December 2017,a total of 123 patients with severe craniocerebral injury were selected in our hospital,and randomly(random number) assigned to the observation group (61 cases) and control group (62 cases).Patients in the control group were given cerebroside-kinin,and patients in the observation group were given cerebroside-kinin and edaravone.The acute physiology and chronic health evaluation score (APACHE Ⅱ),activities of daily living (ADL) score,serum malonaldehyde (MDA),superoxide dismutase (SOD),myeloperoxidase (MPO),matrix metalloprotein 9 (MMP-9),GFAP and UCH-L1 before and after treatment were observed.The side effects were also recorded.Results The APACHE Ⅱ score was significantly reduced in both groups after treatment (P=0.008;P=0.003),and was lower in the observation group than that in the control group (P=0.013).The ADL score of both groups increased after treatment (P=0.025;P=0.008),and was higher in the observation group than that in the control group (P=0.012).After treatment the levels of MDA,SOD and MPO in the observation group were significantly higher than those in the control group (P＜0.05);the level of MMP-9 in the observation group was significantly lower than that in the control group (P=0.012);the levels of GFAP and UCH-L 1 in the observation group were significantly higher than those in the control group (P=0.014;P=0.035).There was no significant difference of the total side effect incidence between the observation group and the control group (8.06％ vs 9.83％,x 2=0.088,P=0.719).Conclusions The treatment by edaravone combined with cerebroside-kinin on severe craniocerebral injury may effectively protect the nerve cells,improve nerve function,clinical efficacy and the body's antioxidant capacity,reduce the serum levels of GFAP,UCH-L1,and have better safety.