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Objective To investigate the effect of 3-n-butylphthalide(NBP)on etoposide-induced senescence in human umbilical vein endothelial cells(HUVECs).Methods HUVECs were divid-ed into blank control group,etoposide group(500 nmol/L etoposide+dimethyl sulfoxide),etopo-side+low-,medium-and high-dose NBP groups(500 nmol/L etoposide+5,10 and 20 μmol/L NBP,respectively).Senescence-related β galactosidase(SA-β-gal)staining was used to observe the change in senescent cell proportion.Real-time quantitative PCR was employed to detect the mRNA levels of senescence-associated secretory phenotype(SASP),such as IL-8,IL-1β,and CXC chemokine ligand 1(CXCL1).Western blotting was applied to measure the expression level of ag-ing-related protein,P21.Immunofluorescence staining was utilized to detect the proportion of pro-liferation-related protein Ki67 positive cells.Results Significantly higher P21 expression(1.00± 0.00 vs 0.59±0.09),larger ratio of SA-β-gal positive cells(29.58±4.51)％vs(11.27±1.18)％,increased mRNA levels of IL-8(2.49±0.11 vs 1.00±0.03),IL-1β(6.32±0.15 vs 1.00±0.03)and CXCL1(2.40±0.24 vs 1.00±0.04),but reduced proportion of Ki67 positive cells(5.95±1.55)％vs(27.38±7.00)％were observed in the etoposide group than the blank control group(P＜0.05).Low-dose NBP treatment decreased the ratio of SA-β-gal positive cells,P21 protein level,and mRNA level of IL-1β,and increased the proportion of Ki67 positive cells when compared with the etoposide group(P＜0.05).Conclusion NBP has an antagonistic effect on etoposide-induced se-nescence of vascular endothelial cells.
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@#Objective To explore the clinical effect of sodium chloride injection of butylphthalide combined with high-frequency repeated transcranial magnetic stimulation(rTMS)in the treatment of limb movement disorders after cerebral infarction.Methods A total of 60 patients with cerebral infarction admitted to the Third People's Hospital of Hubei Province from January to December 2022 were selected,according to the different treatment plans,the patients were divided into basic group and combination group,with 30 cases in each group.The basic group patients were treated with conventional treatment plans,while the combination group patients were treated with butylphthalide sodium chloride injection combined with rTMS.The post-treatment scores of the National Institute of Health stroke scale(NIHSS),activities of daily living(ADL),Fugl-Meyer motor function assessment(FMA),and serum 100β(S100β)were compared between the two groups.Results After treatment,the NIHSS score and serum S100β of patients in the combination group The level is lower than the basic group;The ADL and FMA scores were higher than those of the basic group(P<0.05).Conclusion The combination of sodium butylphthalide chloride injection and rTMS has a significant therapeutic effect on limb movement disorders after cerebral infarction,which can be helpful for the recovery of neurological function in patients and can improve their daily living ability.
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Objective To elucidate the mechanism of dl-3-N-butylphthalide (NBP) on renal ischemia-reperfusion injury (IRI) in rat models. Methods Forty SD rats were randomly divided into the sham operation group (Sham group), model group (IRI group), NF-κB inhibitor pyrrolidine dithiocarbamate group (PDTC group), low-dose NBP group (NBP-L group) and high-dose NBP group (NBP-H group), with 8 rats in each group. Serum creatinine (Scr), serum cystatin C(Cys-C), blood urea nitrogen (BUN) and serum interleukin (IL)-1β and IL-18 levels were detected in all groups. Pathological injury of renal tissues in each group was observed by Hematoxylin-eosin (HE) staining. The expression levels of inflammatory factors and nuclear factor (NF)-κB signaling pathway and cell pyroptosis-related proteins in renal tissues were measured by Western blot and immunohistochemical staining. Results Compared with the Sham group, renal tissue injury was more severe, and the levels of Scr, Cys-C, BUN and serum IL-1β and IL-18 were all up-regulated in the IRI group. Western blot showed that the relative expression levels of NOD-like receptor protein (NLRP3), Gasdermin D(GSDMD), cysteinyl aspartate specific proteinase (Caspase)-1, IL-18, IL-1β, NF-κB p65 and p-NF-κB p65 proteins were all up-regulated, and immunohistochemical staining revealed that the expression levels of NF-κB p65 and p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were all up-regulated in the IRI group. Compared with the IRI group, renal tissue injury was alleviated, and the levels of Scr, Cys-C, BUN and serum IL-18 and IL-1β were down-regulated in the PDTC, NBP-L and NBP-H groups. Western blot showed that the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated, and immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the PDTC, NBP-L and NBP-H groups, respectively. Compared with the NBP-L group, renal tissue injury was mitigated, and the levels of Scr, Cys-C, BUN, serum IL-18 and IL-1β were all down-regulated in the NBP-H group. Western blot showed the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated in the NBP-H group. Immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the NBP-H group. Conclusions NBP may down-regulate the activity of NF-κB/NLRP3 signaling pathway and reduce the expression levels of cell pyroptosis-related proteins and inflammatory factors after renal IRI, thereby suppressing cell pyroptosis and alleviating renal IRI.
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OBJECTIVE To study the improvement effect and possible mechanism of N-butylphthalide on inflammatory injury of bone marrow mesenchymal stem cells （BMSCs） in rats. METHODS BMSCs of rats were divided into control group， model group， N-butylphthalide low-concentration， medium-concentration and high-concentration groups （10， 20， 50 μmol/L）. BMSCs were cultured in vitro and lipopolysaccharide （the final concentration of 10 mg/L） was used to establish the inflammatory injury model. After the intervention of N-butylphthalide， the survival rate， apoptotic rate， the contents of tumor necrosis factor α （TNF- α）， interleukin 1β （IL-1β） and IL-6 in cell culture medium， the mRNA expression of nuclear factor-κB（NF-κB） p65， and the protein expressions of caspase-3， B-cell lymphoma 2 （Bcl-2）， Bcl-2 related X protein （Bax） and NF-κB p65 in cells were detected. RESULTS Compared with control group， the survival rate and protein expression of Bcl-2 were decreased significantly in model group （P＜0.05）； the apoptotic rate， contents of TNF-α， IL-1β and IL-6， the mRNA expression of NF-κB p65， and the protein expressions of caspase-3， Bax and NF-κB p65 were increased significantly （P＜0.05）. Compared with model group， above indexes were significantly reversed in all concentration groups of N-butylphthalide （P＜0.05）， in concentration-dependent manner. CONCLUSIONS N-butylphthalide can ameliorate the inflammatory injury of BMSCs induced by lipopolysaccharide， and its mechanism may be related to the inhibition of NF-κB signaling pathway.
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@#Objective To further update the evidence-based medicine evidence of clinical efficacy and safety of butylphthalide soft capsules in the treatment of Parkinson disease(PD). Methods Randomized controlled trials(RCT) on Butylphthalide soft capsules for PD was collected from PubMed,Embase,Cochrane Library,CNKI,Wanfang and CBM,the retrieval time was from inception to August 2021.The literature selection,data collection were conducted. Meta-analysis was performed by RevMan 5.3 software. Results A total of 28 studies were included and 2463 patients were included. Compared with control group,butylphthalide soft capsules could reduce UPDRS score (MD=-9.52,95%CI -11.23~-7.82,P<0.05),increase MMSE score (MD=3.40,95%CI 2.74~4.06,P<0.05) and MoCA score (MD=3.31,95%CI 3.04~3.57,P<0.05). It also could reduce CRP levels (MD=-2.37,95%CI -2.49~-2.24,P<0.05) and PARK-7 level (MD=-9.39,95%Cl -10.56~-8.22,P<0.05),increase NT-3 levels (MD=8.04,95%CI 7.01~9.07,P<0.05). However,there was no statistical difference in the number of adverse events between the treatment and control groups (RR=1.21,95%CI 0.75~1.94,P=0.43). Conclusion Butylphthalide soft capsules can improve cognitive dysfunction and other complications in Parkinson's patients,by reducing PARK-7,CRP levels and increase NT-3 levels,No serious adverse events have been observed.
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@#Objective To investigate clinical observation of butylphthalide soft capsules combined with rosuvastatin in the treatment of patients with acute cerebral infarction and its influence on serum Lp-PLA2,IL-18,OX40L. Methods From September 2021 to January 2022,we collected 100 patients with acute cerebral infarction who were admitted to the neurology ward and outpatient department of our hospital. These patients were randomly divided into two groups:the control group and the treatment group,with 50 patients in each group. The control group was given basic treatment and rosuvastatin (10 mg/time,1 time/d),while the treatment group was additionally given butylphthalide soft capsule (0.2 g/time,3 times/d). According to the National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index,the degree of neurological deficit and ability of daily life of the two groups were evaluated before and 90 days after treatment,and the levels of serum Lp-PLA2,IL-18,OX40L were compared. Results The total clinical efficacies in the treatment group were 94.00%,higher than 80.00% in the control group(P<0.05). After 90 d treatment,NIHSS score and Lp-PLA2 level decreased,Barthel index increased,and the improvement in the treatment group was significantly better than those in the control group (P<0.05). The level of serum Lp-PLA2 was higher in patients with high NIHSS scores in the treatment group than in patients with low NIHSS scores. Before treatment,there were no significant differences between the two groups in NIHSS score,Barthel index,IL-18 levels,and OX40L levels. After treatment,there were also no significant differences between the two groups in IL-18 and OX40L levels (P>0.05). The incidence of adverse reactions in the two groups was 12.00% and 16.00%,respectively(P>0.05). Conclusion The combination of butylphthalide soft capsule and rosuvastatin has good efficacy and safety,which can significantly promote the recovery of neurological function,improve the ability of daily life,and reduce the level of serum Lp-PLA2.
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Objective To investigate the effects of butylphthalide soft capsule on the expression of uric acid and the pathological changes of white matter in patients with moderate and severe leukoaraiosis.Methods A total of 60 patients with moderate to severe leukoosteoporosis admitted to the department of neurology of People's Hospital of Hai'an City,Jiangsu province from May 2021 to November 2022 were selected and divided into a study group and a control group by random number table method.The control group was treated with conventional basic treatment,and the study group was treated with butylphthalein softgel based on the control group.The score of mini-mental state examination(MMSE)scale,montreal cognitive assessment(MoCA)scale,hachinski ischemia score(HIS)scale,total decline scale(GDS),the levels of plasma factors[homocysteine(Hcy),total cholesterol(TC),central nervous specific protein(S100β)and uric acid(UA)]and improvement in leukoencephalopathy[as measured by arterial flow velocity at peak systolic flow rate(Vs),end-diastolic peak flow rate(Vd),and mean peak flow rate(Vm)]before and after treatment were compared between the two groups.Results A total 60 patients with leukoaraiosis were included,with 30 cases in the study group and 30 cases in the control group,respectively.Before treatment,there were no significant differences in scores of MMSE,MoCA,HIS and GDS,levels of Hcy,TC,S100β and UA,Vs,Vd,and Vm between the two groups(P＞0.05).After treatment,the scores of MMSE and MoCA scores,Vs,Vd,and Vm on both sides were significantly higher than those before treatment(P＜0.05),and those in the study group was significantly higher than those in the control group(P＜0.05);the scores of HIS and GDS,and the levels of Hcy,TC,S100β and UA were significantly lower than those before treatment(P＜0.05),and those in the study group was significantly lower than those in the control group(P＜0.05).Conclusions Butylphthalide soft capsule in the treatment of moderate and severe leukoaraiosis can effectively reduce the cognitive impairment,restore the cognitive function,reduce the levels of plasma factors,improve the cerebral blood flow,and improve the condition of leukoaraiosis.
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Objective To investigate the efficacy and safety of Urinary kallidinogenase(UK)combined with butylphthalide in patients with acute cardioembolic stroke(ACS).Methods A retrospective collection was performed for ACS patients diagnosed and treated in Hangzhou First People's Hospital from May 2022 to April 2023.According to the treatment protocol,ACS patients were divided into UK group and Butylphthalide+UK group.The clinical efficacy,neurological function,serum indexes(Hcy,NT-proBNP and VEGF)and prognosis of the two groups were compared after 2 weeks of treatment.Results A total of 86 ACS patients were included in the study,including 43 in the UK group and 43 in the Butylphthalide+UK group.After treatment,the total effective rate of treatment in the Butylphthalide+UK group was significantly higher than that in the UK group(P<0.05),and there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).In addition,the expression levels of Hcy and NT-proBNP in ACS patients in the Butylphthalide+UK group were significantly lower than those in the UK group(P<0.05),while the expression levels of VEGF were significantly higher than those in the UK group(P<0.05).The NIHSS score and mRS score of ACS patients in the Butylphthalide+UK group were significantly lower than those in the UK group(P<0.05).The rate of collateral circulation establishment in the Butylphthalide+UK group was significantly higher than that in the UK group(P<0.05).Conclusion Butaphthalide combined with UK has significant efficacy and high safety in ACS patients,which may be achieved by regulating the expression levels of serum Hcy,NT-proBNP and VEGF,thereby improving neurological function and promoting the establishment of collateral circulation.
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Objective:To investigate the effects of butylphthalide combined with ozagrel sodium on the National Institutes of Health Stroke Scale (NIHSS) score, activities of daily living (ADL) score, and coagulation function in patients with acute cerebral infarction.Methods:Ninety-four patients with acute cerebral infarction who were admitted to Gujiao Medical Group Central Hospital from January 2019 to November 2021 were included in this study. They were randomly assigned to undergo treatment with either ozagrel sodium (control group, n = 47) or butylphthalide combined with ozagrel sodium (observation group, n = 47) for 14 consecutive days. Before and after treatment, NIHSS score, ADL score, coagulation function (thrombin time, prothrombin time, D-dimer, activated partial thrombin time), bilateral middle cerebral artery blood flow status (mean blood flow velocity (Vm), resistance index, pulsatility index), brain tissue damage factor (brain natriuretic peptide, neuron-specific enolase, S100 β protein) and the incidence of adverse drug reactions were compared between the two groups. Results:Before treatment, there were no significant differences in NIHSS and ADL scores between the two groups (both P > 0.05). After treatment, the NIHSS score was significantly lower in the observation group than that in the control group [(8.70 ± 1.62) points vs. (9.45 ± 1.2) points, t = 2.51, P < 0.05]; the ADL score was significantly higher in the observation group than that in the control group [(65.15 ± 7.41) points vs. (61.20 ± 6.32) points, t = 2.78, P < 0.05]. Before treatment, there were no significant differences in thrombin time, prothrombin time, D-dimer, and activated partial thrombin time between the two groups (all P > 0.05). After treatment, thrombin time, prothrombin time, and activated partial thrombin time were significantly higher in the observation group than those in the control group ( t = 4.34, 3.00, 2.63, all P < 0.05). After treatment, D-dimer level in the observation group was significantly lower than that in the control group ( t = 3.39, P < 0.05). Before treatment, mean blood flow velocity, resistance index, and pulsatility index were similar between the two groups (all P > 0.05). After treatment, the mean blood flow velocity in the observation group was significantly higher than that in the control group ( t = 3.23, P < 0.05). The pulsatility index and resistance index were significantly lower in the observation group than those in the control group ( t = 2.14, 3.16, both P < 0.05). Before treatment, there were no significant differences in brain natriuretic peptide, neuron-specific enolase, and S100 β protein levels between the two groups (all P > 0.05). After treatment, brain natriuretic peptide, neuron-specific enolase, and S100 β protein levels in the observation group were significantly lower than those in the control group ( t = 3.09, 2.18, 3.33, all P < 0.05). There was no significant difference in incidence of adverse reactions between the observation and control groups [6.38% (3/47) vs. 2.13% (1/47), P > 0.05]. Conclusion:Butylphthalide combined with ozagrel sodium for the treatment of acute cerebral infarction can reduce neurological dysfunction and brain tissue injury, and improve coagulation function, hemodynamic state of the middle cerebral artery, and activities of daily life, without increasing adverse reactions.
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Objective:To investigate the clinical efficacy of butylphthalide combined with hyperbaric oxygen therapy on post-stroke cognitive impairment in patients with acute ischemic stroke.Methods:A total of 90 patients with post-stroke cognitive impairment who were hospitalized within 72 hours of onset in Suining County People's Hospital from December 2019 to November 2020 were included in this study. They were randomly divided into a control group and an observation group ( n = 45/group). The control group was given conventional treatment and the observation group was given butylphthalide combined with hyperbaric oxygen therapy in addition to conventional treatment. The National Institutes of Health Stroke Scale score, Montreal Cognitive Assessment score, and Activities of Daily Living score were compared between the two groups before and after treatment. Results:Before treatment, there were no significant differences in the National Institutes of Health Stroke Scale score, Montreal Cognitive Assessment score, and Activities of Daily Living score between the two groups (all P > 0.05). At 14 days and 1 month after surgery, the National Institutes of Health Stroke Scale scores in the observation group were (4.02 ± 2.18) points and (3.21 ± 2.03) points, which were significantly lower than (5.21 ± 2.24) points and (4.62 ± 2.68) points in the control group ( t =2.55, 2.81, both P < 0.05). At 1 and 3 months after treatment, the Montreal Cognitive Assessment score in the observation group were (19.79 ± 5.67) points and (23.69 ± 2.67) points, which were significantly higher than (16.88 ± 5.12) points and (19.74 ± 2.29) points in the control group ( t = 2.56, 7.53, both P < 0.05). At 1 and 3 months after treatment, Activities of Daily Living scores in the observation group were (54.85 ± 5.69) points and (74.38 ± 4.98) points, which were significantly higher than (46.78 ± 6.24) points and (63.21 ± 5.24) points in the control group ( t = 6.41, 9.76, both P < 0.05). Conclusion:Butylphthalide combined with hyperbaric oxygen therapy for the treatment of post-stroke cognitive impairment in patients with acute ischemic stroke can alleviate neurologic deficits, and improve cognitive function and the ability of daily life.
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Objective:To investigate the therapeutic effect of dl-3-n-butylphthalide on dysphagia after cerebral infarction.Methods:Seventy acute cerebral infarction patients with dysphagia who received treatment in The First People's Hospital of Huzhou from December 2019 to December 2020 were included in this study. They were randomly assigned to receive either routine treatment combined with swallowing function training (routine treatment group, n = 35) or intravenous dl-3-n-butylphthalide, routine treatment, and swallowing function training in combination (dl-3-n-butylphthalide treatment group, n = 35). All patients received 2 weeks of treatment. Clinical efficacy and swallowing function training pre- and post-treatment were compared between the two groups. Results:Total response rate was significantly higher in the dl-3-n-butylphthalide treatment group than in the routine treatment group [100.0% (35/35) vs. 91.4% (32/35), χ2 = 1.39, P = 0.238]. Before treatment, there were no significant differences in the scores of the Water-Swallowing Test and the Standardized Swallowing Assessment between the two groups ( P = 0.898, 0.691). The scores of the Water-Swallowing Test and the Standardized Swallowing Assessment measured after treatment in the dl-3-n-butylphthalide treatment group were (0.68 ± 0.76) points and (21.60 ± 2.50) points, which were significantly lower than those in the routine treatment group [(1.15 ± 0.77) points, (27.62 ± 3.80) points, t = 2.57, 7.82, P = 0.012, < 0.001]. Conclusion:Dl-3-n-butylphthalide treatment is highly effective on dysphagia after acute cerebral infarction. It can effectively promote the recovery of a patient's swallowing function. The treatment method is worthy of clinical application.
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Objective:To investigate the clinical efficacy and safety of Butylphthalide combined with Donepezil in the treatment of vascular dementia.Methods:A total of 214 patients with vascular dementia admitted to our hospital from December 2018 to December 2020 were divided into control(n=107)treated with Donepezil tablets, and study group(n=107)treated with Butylphthalide capsule plus Donepezil tablets in a multicenter single-blind randomized control trial.Clinical efficacy, dementia degree, cognitive function, behavioral ability, homocysteine(Hcy), brain-derived neurotrophic factor(BDNF), glial fibrillary acidic protein(GFAP)and neuron-specific enolatase(NSE)expression were compared between the two groups before versus after 24 weeks of treatment.And their safety was also evaluated.Results:The total effective rate was statistically significantly higher in study group than in the control group(93.46% and 80.37%, χ2=8.054, P<0.05). The scores of Hasegawa Dementia Scale(HDS), mini mental state examination scale(MMSE)and blessed Behavior Scale(BBS)in the treatment group before treatment were(17.2±2.4)points, (19.0±2.2)points and(25.1±1.8)points respectively; After 24 weeks of treatment, the scores in the treatment group were(27.4±2.8)points, (26.8±1.9)points and(14.2±2.7)points respectively; Before treatment, the scores in control group were(17.4±2.0)points, (18.6±2.1)points and(25.4±1.7)points respectively; After 24 weeks of treatment, the scores in control group were(21.8±3.3)points, (22.3±1.6)points and(19.5±2.3)points respectively.Hcy, BDNF, GFAP and NSE in the treatment group before treatment were(34.5±4.3)μmol/L、(3.5±0.4)μg/L、(13.2±0.8)μg/L and(18.9±1.7)μg/L; After 24 weeks of treatment, the scores in treatment group were(15.9±2.9)μg/L respectively μmol/L、(5.3±0.3)μg/L、(9.7±0.6)μg/L and(18.9±1.7)μg/L; Before treatment, the scores in control group were(35.3±4.4)μmol/L、(3.4±0.4)μg/L、(13.1±0.9)μg/L and(19.2±1.3)μg/L; After 24 weeks of treatment, the scores in control group was(23.3±4.9)μmol/L、(4.5±0.4)μg/L、(10.8±0.7)μg/L and(14.3±2.1)μg/L respectively.Before treatment, there was no significant difference in the expression of HDS scale, MMSE score, BBS score, Hcy, BDNF, GFAP and NSE between the two groups of patients with vascular dementia( t=0.662, 1.360, 1.253, 1.345, 1.829, 0.859, 1.450, all P>0.05); After treatment 24 weeks, the ADAS-Cog score, BBS score, Hcy, GFAP and NSE expressions of the two groups of vascular dementia patients were lower than that before treatment, while the HDS scale score, MMSE score and BDNF expression were higher than that before treatment(in treatment group: t=34.746, 31.273, 36.204, 36.289, 28.610, 27.256, 37.239; in control group: t=21.339, 18.849, 20.866, 20.522, 11.795, 14.497, 20.115, all P<0.05), the differences were statistically significant; After treatment for 24 weeks, the BBS score, Hcy, GFAP and NSE expression in the treatment group were lower than in control group, while the HDS scale score, MMSE score and BDNF expression were higher than in control group( t=15.457, 11.623, 16.551, 12.342, 13.385, 18.740, 11.547, all P<0.05), the differences were statistically significant.In the control group, there were 2 cases of mild gastrointestinal reaction and 3 cases of dizziness, with the incidence of 4.67%; Slight gastrointestinal reaction occurred in 4 cases and dizziness in 5 cases in the treatment group, with an incidence of 8.41%.There was no significant difference in the incidence of adverse reactions between the two groups( χ2=1.223, P>0.05). Conclusions:Butylphthalide soft capsules combined with Donepezil hydrochloride tablets have significant clinical effects on patients with vascular dementia, effectively reduce the degree of dementia, and improve the cognitive function and behavioral ability of patients, with good security.Therefore, it is worthy of clinical promotion.
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Aim To explore the mechanism of Huoxue Rongluo reeipe in promoting angiogenesis after ischemic stroke based on the correlation between mir-370-3p and JAK2/STAT3 pathway.Methods Hats were randomly divided into six groups.MCAO/R method was used to establish the model.After seven days of intragastrie administration,the expressions of CD31 ,vWF and vascular endothelial growth factor ( VEGF) in brain tissue were observed by immunofluorescence stai- ning; the expression of JAK2 ,p-jak2,STAT3 and p- STAT3 in brain tissue was detected by Western blot; J the expressions of JAK2,STAT3 mRNA and mir-370- 3p in brain tissue were detected by real-time PCR f RT-PCR) ; the correlation between mir-370-3p and JAK2/STAT3 pathway was analyzed by Pearson correlation ; the expressions of lncma-hl9 and mir-370-3p were detected by real-time quantitative PCR ( RT qPCR) ; the targeting relationship between lncrna-hl9 and mir-370-3p was detected by luciferase reporter assay.Results Huoxue Rongluo decoction could increase the microvessel density and average fluorescence intensity of VEGF,up-regulate JAK2 and STAT3 mR- NA,down-regulate the expression of mir-37()-3p,and promote the expressions of JAK2,p-jak2 ,STAT3 and p- STAT3.Mir-370-3p was highly negatively correlated with JAK2 and STAT3 mRNA respectively,which could be reversed by stattic,an inhibitor of STAT3 SH2 domain.Conclusions Huoxue Rongluo recipe may stimulate angiogenesis after ischemic stroke by down- regulating the expression of mir-370-3p,activating JAK2 / STAT3 pathway and promoting the expression of downstream VEGF,so as to improve the symptoms of neurolo.
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Objective:To investigate the effect of Naoxintong capsule combined with butylphthalide injection on inflammatory factors, oxidative stress response and hemorheology in patients with acute cerebral infarction. Methods:Eighty-six patients with acute cerebral infarction who received treatment in Zhuji Hospital of Traditional Chinese Medicine from December 2017 to December 2019 were included in this study. Thrombolysis and thrombectomy were contraindicated in these patients. They were randomly assigned to receive treatment either with butylphthalide injection (control group, n = 43) or butylphthalide injection and Naoxintong capsule (observation group, n = 43) for 2 weeks. Therapeutic effects, Barthel Index, inflammatory factors (C-reactive protein, intercellular adhesion molecule-1 and interleukin-6), oxidative stress response (malondialdehyde and superoxide dismutase) and hemorheology (whole blood viscosity at high and low shear rates, plasma viscosity and fibrinogen) were compared between the two groups. Results:Total effective rate in the observation group was significantly higher than that in the control group (93.02% vs. 72.09%, χ2 = 6.541, P < 0.05). After treatment, Barthel Index in the observation group was significantly higher than that in the control group [(61.51 ± 5.24) points vs. (50.43 ± 4.81) points, t = 10.215, P < 0.05). After treatment, serum levels of C-reactive protein, intercellular adhesion molecule-1, and interleukin-6 in the observation group were (4.42 ± 1.03) mg/L, (84.23 ± 5.05) μg/L and (94.33 ± 10.22) μg/L, respectively, which were significantly lower than those in the control group [(8.32 ± 1.71) mg/L, (103.51 ± 6.35) μg/L, (118.92 ± 13.31) μg/L, t = 12.810, 15.583, 9.609, all P < 0.05]. After treatment, serum malondialdehyde level in the observation group was significantly lower than that in the control group [(3.76 ± 0.78) μmol/L vs. (4.94 ± 0.90) μmol/L, t = 6.497, P < 0.05]. Serum superoxide dismutase level in the observation group was significantly higher than that in the control group [(35.76 ± 2.65) U/L vs. (30.34 ± 2.11) U/L, t = 10.492, P < 0.05]. After treatment, whole blood viscosity at high and low shear rates, plasma viscosity and fibrinogen levels in the observation group were (4.10 ± 0.51) mPa · s, (9.31 ± 1.36) mPa · s, (1.24 ± 0.26) mPa · s and (2.71 ± 0.40) g/L respectively, which were significantly lower than those in the control group [(5.72 ± 0.76) mPa · s, (11.49 ± 1.59) mPa · s, (2.21 ± 0.32) mPa · s and (3.92 ± 0.54) g/L, t = 11.607, 6.832, 15.427 11.807, all P < 0.05). Conclusion:Naoxintong capsule combined with butylphthalide injection is highly effective in the treatment of acute cerebral infarction. It can reduce inflammatory reaction and improve oxidative stress response and hemorheological changes.
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Objective To investigate the effects of butylphthalide on serum S-100 beta protein,NSE and neurological deficits in patients with cerebral infarction and reperfusion.Methods From January 2016 to January 2018,104 patients with early cerebral infarction admitted to the People's Hospital of Feicheng were divided into two groups according to different treatment methods.The control group (n =52) was given routine treatment,while the observation group (n =52) was given butylphthalide treatment on the basis of the control group.The degree of neurological deficit,serum NSE and S-100 beta protein levels were compared between the two groups before and after thrombolysis.Results The NIHSS scores of the two groups before thrombolysis were (10.27 ± 1.32) points and(10.28 ± 1.30) points,respectively,the difference between the two groups was no statistically significant(t =0.038,P ＞ 0.05).The NIHSS scores of the two groups were decreased at 24h and 7d after thrombolysis,which of the observation group at 24h and 7d after thrombolysis were (8.32 ± 1.37)points and (4.25 ± 1.54)points,respectively,which were significantly lower than those of the control group [(9.24 ± 1.40) points and (9.50 ± 1.24) points],the differences were statistically significant (t =3.396,19.147,all P ＜ 0.05).The serum NSE levels of the two groups before thrombolysis were (22.56 ± 5.78) U/mL and (22.58 ± 5.77) U/mL,respectively,the difference between the two groups was no statistically significant (t =0.017,P ＞ 0.05).At 24h and 7d after thrombolysis,the serum NSE levels of the two groups were decreased.The serum NSE levels of the observation group at 24h and 7d after thrombolysis were (15.08 ± 9.35) U/mL and (13.25 ± 6.47) U/mL,respectively,which were significantly lower than those in the control group [(18.96 ± 10.14)U/mL and (16.98 ± 7.11) U/mL],the differences were statistically significant(t =2.028,2.79,all P ＜ 0.05).The serum S-100β protein levels in the two groups before thrombolysis were(1.26 ± 0.71)μg/L and (1.27 ± 0.70)μg/L,respectively,and the difference was not significant (t =0.0723,P ＞0.05).At 24h and 7d after thrombolysis,the serum S-100β protein levels were decreased in both two groups,which in the observation group were (1.13 ± 0.62) μg/L and (0.53 ± 0.48) μg/L,respectively,which were significantly lower than those in the control group [(1.40 ± 0.64) μg/L,(0.87 ± 0.32) μg/L],the differences were statistically significant (t =2.185,4.25,all P ＜ 0.05).Conclusion Butylphthalide injection for patients with cerebral infarction and reperfusion can effectively promote the recovery of neurological function,improve the levels of serum NSE and S-100 beta protein,and help patients recover as soon as possible.
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Objective: To observe the effects of butylphthalide on cerebral ischemia-reperfusion injury in rats. Methods: We divided 90 SD rats into sham-operation group, model group, low-dose butylphthalide group, medium-dose butylphthalide group, high-dose butylphthalide group, and ATRA group. Neurological impairment score (NDS) was used to evaluate neurological function. TTC staining was used to calculate the volume of ischemic brain tissue. The xanthine oxidase method was used to detect SOD. The thiobarbituric acid colorimetry was used to detect MDA. ELISA was used to detect IL-6 and TNF-α expressions. The Real-time PCR was used to detect HO-1 gene expression. Western blot was used to detect Nrf2 and HO-1 protein expressions. Results: In low-, medium-, and high-butylphthalide groups, the NDS; volume of ischemic brain tissue; expressions of MDA, IL-6 and TNF-α; 2-△△Ct value of HO-1; protein expressions of Nrf2 and HO-1 were lower than those in model group (P<0.05), but SOD expression was higher than that in model group (P<0.05). The NDS; volume of ischemic brain tissue; expressions of MDA, IL-6 and TNF-α; 2-△△Ct value of HO-1; protein expressions of Nrf2 and HO-1 decreased in a dose-depended manner in low-, medium-, and high-butylphthalide groups, and SOD expression was increased in a dose-depended manner (P<0.05). Conclusion: Butylphthalide can play an antioxidant role by up-regulating Nrf2/HO-1 pathway, which benefits neuroprotective function in cerebral ischemia-reperfusion rats.
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Butylphthalide and ferulic acid exhibit excellent therapeutic effects in ischemic stroke. In this research, twelve 3-n-butylphthalide derivatives were designed by molecular hybridization strategy. The target compounds were obtained by nucleophilic substitution, reduction reaction, esterification reaction and elimination reaction, and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The compounds with the best neuroprotective activity were biologically evaluated for their ability to inhibit platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) via the Bron method．The results indicate that 7b exhibited potent neurocyte protective activity as well as prominent anti-platelet aggregation activity. Compound 7b has potential to be developed as a drug for ischemic stroke.
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Objective: To study the content variation and chemical composition of Siwu Decoction between mixed decoction and single decoction comprehensively, and then explore variation rule of Siwu Decoction by different decocting methods based on material basis. Methods: Components of Siwu Decoction were identified by LC-MS/MS and an UPLC wavelength switching method for simultaneously determining the contents of multiple compounds in Siwu Decoction was established based on the idea of TCM chemistry holography. The mixed and single decoction samples were prepared and tested. Experimental data was compared to analyze material basis differences and variation rule of Siwu Decoction by different decocting methods. Results: A total of 72 compounds were identified and assigned, 18 compounds were quantitative detected and all of 18 analytes showed good linearity (R2 ≥ 0.999) within the test range. The relative standard deviations of the precision, repeatability and stability were not exceeding 2.0%, and the recoveries were in the range of 97%-105%. Analysis of Siwu Decoction samples showed dissolution of ligustilide, 3-n- butylphthalide, catechin, gallic acid and paeoniflorin was affected by the change of solvent volume and dissolution of aucubin, catechin, oxypaeoniflorin, paeoniflorin and acteoside were higher in mixed decoction than single decoction obviously. Compared to single decoction, the kinds of compounds in mixed decoction did not change significantly but the content showed notable variety. Conclusion: Through the study of chemistry holography, the composition and content of compounds in TCM mixed decoction and herbs single decoction can be compared and analyzed comprehensively to provide a new perspective for the study on the rule of TCM decoction and dissolution. TCM chemistry holography study may become a useful exploration of the TCM quality study.
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@#Objective To explore the clinical effect of dl-3-N-butylphthalide（NBP）injection combined with antiplatelet drug therapy and the influence on stroke recurrence of minor stroke patients. Methods A retrospective analysis was performed on 95 patients with minor stroke that admitted to the stoke center of the second affiliated hospital of Harbin Medical University from January to July 2019.It included 45 patients in the combined treatment group （NBP plus antiplatelet treatment group） and 50 patients in the control group （antiplatelet treatment group）. The mRS score，NIHSS score and BI of the two groups were analyzed at 14 days，1 month，3 months and 6 months after treatment. The stroke recurrence events at 1 month，3 months，and 6 months after treatment in both groups will be recorded too. We used multivariate analysis to analyze the factors that might influence stroke recurrence in minor stroke patients. Results ①There was no significant difference in baseline information between the two groups（P>0.05），which was comparable. ②At 14 days，1 month，3 months and 6 months after treatment，the mRS scores and NIHSS scores of the patients in the two groups were significantly lower than that at admission，while the Barthel index were significantly higher than that at admission （P<0.01）. ③In the combined treatment group at 1 month，3 months and 6 months after treatment，the mRS scores were significantly lower than those in the control group （P=0.033，0.031，0.013）. ④The number of the combined treatment group patients with stroke recurrence at 3 months and 6 months after treatment was significantly lower than that in the control group（P=0.033，0.039）. ⑤The results of multivariate analysis showed that using NBP was an independent protective factor in stroke recurrence at 3 months （OR=0.060，95%CI 0.005～0.778，P=0.031） and 6 months （OR=0.163，95%CI 0.028～0.968，P=0.028） for minor stroke. Conclusion NBP combined with antiplatelet drugs can significantly improve the neurological function and reduce the stroke recurrence of minor stroke patients.
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@#Objective To study the effects of butylphthalide injection on different OCSP types of acute cerebral infarction（ACI） and its effect on hypersensitive c-reactive protein（Hs-CRP） and FIB. Methods Two hundred and forty-eight ACI patients admitted to our hospital were randomly divided into control group（n-113） and observation group（n=135），The observation group was treated with additional butylphthalide injection. All patients received OCSP typing at the time of admission，and at the same time，NIHSS score，Hs-CRP and FIB were measured at the time of admission and 2 weeks later. The changes of Hs-CRP and FIB were compared between the two groups in terms of overall efficacy and different subtypes. Results After 2 weeks of treatment，NIHSS score，Hs-CRP and FIB levels of the observation group were significantly lower than those of the control group （P<0.05），and the overall effective rate of the observation group was higher than that of the control group （P<0.05）；The NIHSS score and FIB level of TACI，PACI，POCI and LACI was significantly lower in observation group than control group after 2 weeks（P<0.05）；TACI and POCI curative effect of observation group is better than that of control group （P<0.05），while there was no statistically significant difference between the PACI and LACI groups and the control group （P>0.05）；NIHSS score was positively correlated with Hs-CRPand FIB.Conclusion The curative effect of butylphthalide injection is rather good for all OCSP types of ACI，especially for TACI and POCI，and butylphthalide injection can effectively reduce the inflammatory response. The mechanism may be to achieve therapeutic effect by reducing the inflammatory response.