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Objective To evaluate the effect of dexmedetomidine administered at different time points on the quality of anesthesia recovery and inflammatory response in children undergoing craniotomy.Methods According to the randomized double-blind method,200 pediatric patients who underwent craniotomy in Beijing Fengtai Hospital from August 2017 to August 2022 were divided into 4 groups,with 50 cases in each group.In preoperative group,0.5μg/(kg?h)dexmedetomidine was intravenously pumped 30min before anesthesia induction,and the drug was stopped before the start of surgery.In intraoperative group,0.5μg/(kg?h)dexmedetomidine was infused intravenously after the beginning of the operation,and the drug was stopped 30min before the end of the operation.In postoperative group,0.5μg/(kg?h)dexmedetomidine was infused intravenously after the main steps of the operation,and the drug was discontinued at the end of the operation.In control group,the same volume of normal saline was injected intravenously 30min before anesthesia induction.The recovery quality,hemodynamics,inflammatory response,and adverse reactions were compared among the four groups.Results The extubation time of postoperative group[(43.84±5.12)min]was significantly longer than that of preoperative group[(16.73±3.28)min],intraoperative group[(18.05±3.47)min],and control group[(25.63±4.64)min],the difference was statistically significant(P<0.05).Ramsay sedation scores,mean arterial pressure(MAP),heart rate(HR),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 were compared between preoperative group and intraoperative group before anesthesia induction in a quiet state(T0),immediately after extubation(T1)and 5min after extubation(T2).The difference was not statistically significant(P>0.05).Ramsay sedation scores and levels of CRP,TNF-α and IL-6 at T1 and T2 in postoperative group were significantly higher than those in preoperative group,intraoperative group and control group,and MAP and HR were significantly lower than those in preoperative group,intraoperative group and control group,with statistically significant differences(P<0.05).There was no significant difference in the overall incidence of adverse reactions among the four groups(P>0.05).Conclusion Intravenous infusion of dexmedetomidine at different time points in children undergoing craniotomy has no obvious adverse reactions,but intravenous infusion of dexmedetomidine before and during operation has little effect on hemodynamics and inflammatory response during anesthesia recovery period,and the quality of recovery and sedation is better.Intravenous infusion of dexmedetomidine after operation will prolong extubation time.
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Objective To evaluate the effects of leptin on brain injury and long-term cognitive function in rats undergoing orthotopic liver transplantation. Methods Ninety clean-grade male Sprague-Dawley rats, aged 3 months, weighing 200-250 g, were divided into 3 groups by a random number table method: sham operation group ( S group) , liver ischemia-reperfusion ( I∕R) group ( I∕R group) and lep-tin group ( L group) , with 18 rats in each group. Orthotopic liver transplantation was performed to estab-lish the model of liver I∕R injury in I∕R and L groups. Leptin 1 mg∕kg was intraperitoneally injected at the onset of ischemia in L group, and the equal volume of normal saline was given instead of leptin in S and I∕R groups. Twelve rats in each group were sacrificed at 3 days after operation, and brains were removed for ex-amination of the pathological changes in hippocampal CA1 region ( with a light microscope) and for determi-nation of apoptosis in hippocampal neurons ( by TUNEL assay) and expression of aquaporin 4 ( AQP4) and protein kinase C ( PKC) in the hippocampus ( by Western blot) . The apoptosis rate was calculated. The remaining 6 rats in each group underwent a Morris water maze test at 30 days after surgery to evaluate long-term cognitive function. Results Compared with S group, the apoptosis rate of hippocampal neurons was significantly increased, the expression of AQP4 and PKC was up-regulated, the escape latency was pro-longed, and the time of staying at the platform quadrant was shortened in I∕R and L groups (P<0. 05). Compared with I∕R group, the apoptosis rate of hippocampal neurons was significantly decreased, the ex-pression of AQP4 and PKC was down-regulated, the escape latency was shortened, and the time of staying at the platform quadrant was prolonged in L group (P<0. 05). Conclusion Leptin can reduce the brain damage in rats undergoing orthotopic liver transplantation, the mechanism may be related to down-regulating the expression of PKC and AQP4, and leptin can also improve long-term cognitive function after orthotopic liver transplantation in rats.
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Objective To investigate the effect of dexmedetomidine (DEX) on brain injury and long-term cognitive dysfunction in rats after orthotopic liver transplantation ischemia/reperfusion and its mechanism. Methods Fifty-four male Sprague-Dawley (SD) rats were randomly divided into sham-operated group (n=18), orthotopic liver transplantation ischemia/reperfusion group (I/R group, n=18) and DEX pre-administration group (DEX group, n=18). The orthotopic liver transplantation ischemia/reperfusion models were established in I/R group and DEX group. Rats of the DEX group were intraperitoneally injected with DEX 100 μg/kg 30 min before the incision, and an equal volume of normal saline was injected into rats of the sham-operated group and I/R group at the same time. Twelve rats in each group were sacrificed 3 d after operation and brain tissues were taken. The pathological changes of the hippocampus were observed under light microscope. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to detect neuronal apoptosis index of the hippocampus. Western blotting was used to detect the protein levels of aquaporin 4 (AQP4) and protein kinase C (PKC) in the hippocampus. The remaining 6 rats accepted Morris water maze test to evaluate the long-term cognitive function 30 d after surgery. Results As compared with those in the sham-operated group, rats in the I/R group and DEX group had hippocampus edema and disordered cell arrangement; as compared with sham-operated group, I/R group and DEX group had significantly increased neuronal apoptosis index, significantly increased protein levels of AQP4 and PKC, significantly shorter quadrant retention time of the platform, and statistically longer escape latency (P<0.05). As compared with those in the I/R group, the pathological damage of hippocampal neurons was significantly alleviated, the neuronal apoptosis index was significantly decreased, the protein levels of AQP4 and PKC were statistically decreased, and the residence time of the quadrant in the platform was significantly prolonged, and the escape latency was statistically shorter in DEX group (P<0.05). Conclusion Pre-administration of DEX may reduce the brain damage and improve long-term cognitive dysfunction in rats after orthotopic liver transplantation ischemia/reperfusion, which may be related to down-regulating the AQP4 and PKC expression levels and reducing neuronal apoptosis.
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Objective To investigate the effect of dexmedetomidine (DEX) on platelet activating factor (PAF) levels in the plasma and hippocampus of mice with postoperative cognitive dysfunction (POCD).Methods A total of 30 specific pathogen free C57BL/6J mice were randomly divided into three groups (n=10):sham-operated group,POCD group and DEX intervention group.Mice in sham-operated group only received anesthesia but not partial hepatectomy surgery;the POCD models of POCD group and DEX intervention group were established by partial hepatectomy surgery under anesthesia;DEX (25 μg/kg) was given to mice from the DEX intervention group by intraperitoneal injection 30 min prior to partial hepatectomy surgery;normal saline of the same volume was injected intraperitoneally prior to partial hepatectomy surgery in sham-operated group and POCD group.Behavioral test was performed via fear conditioning tests (FCS),and the percentage of freezing time was recorded on the 3rd d of POCD modeling.The PAF levels in the blood and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA).Results (1) As compared with the sham-operated group,POCD group had significantly lower percentage of freezing time in audible alerts on FCS (57.3％±9.1％ vs.30.0％±5.4％,P＜0.05);as compared with the POCD group,DEX intervention group had significantly higher percentage of freezing time in audible alerts on FCS (30.0％±5.4％ vs.46.5％±6.6％,P＜0.05).(2) The PAF levels in the plasma and hippocampus of POCD group were significantly increased as compared with those in the sham-operated group ([0.5±0.3] ng/mL vs.[22.5±2.2] ng/mL;[5.7±1.0]ng/mL vs.[9.8±1.4] ng/mL],P＜0.05);the PAF levels in the plasma and hippocampus of DEX intervention group were significantly increased as compared with those in the POCD group ([22.5±2.2] ng/mL vs.[14.6±1.6] ng/mL;[9.8±1.4] ng/mL vs.[7.4±1.2] ng/mL,P＜0.05).Conclusion DEX can improve early POCD in mice after partial hepatectomy surgery by reducing PAF levels in the plasma and hippocampus.
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Objective To investigate the effect of dexmedetomidine (DEX) on mammalian target of rapamyein (mTOR) signaling pathway in the hippocampus of mice with postoperative cognitive dysfunction (POCD).Methods A total of 64 specific pathogen free (SPF) adult C57BL/6J mice were randomly divided into four groups (n=16):sham-operated group,POCD group,DEX-L group (giving low dose of DEX) and DEX-H group (giving high dose of DEX).Mice only received anesthesia but not partial hepatectomy surgery in sham-operated group;mouse models of POCD in POCD group were established by partial hepatectomy surgery under anesthesia;DEX (25 μg/kg or 50 μg/kg) was given by intraperitoneal injection 30 min prior to partial hepatectomy surgery,and then,the mouse models of POCD were established in DEX-L group and DEX-H group;normal saline of the same volume was injected intraperitoneally prior to partial hepatectomy surgery in sham-operated group and POCD group.Behavioral test was performed via Fear Conditioning Test (FCS) one d before surgery and 3 d after surgery for training and behavioral testing,and the percentage of freezing time was recorded.Enzyme linked immunosorbent assay (ELISA) was used to detect the protein levels of beta amyloid protein 42 (Aβ-42) and phosphorylated(p)-tau-181 in cerebrospinal fluid of mice 3 d after surgery.The hippocampus tissues of mice were collected 3 d after surgery,and the mRNA expressions of mTOR,Tau,nuclear factor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) in hippocampal tissues were tested by reverse transcription-polymerase chain reaction (RT-PCR).The protein expressions ofmTOR,p-tau (pS396 Tau protein),NF-κB and TNF-α in hippocampal tissues were tested by Westem blotting.Results (1) As compared with that in sham-operated group,the percentage of freezing time in conditioning FCS in POCD group was statistically lower (P＜0.05);as compared with that in POCD group,the percentage of freezing time in conditioning FCS in DEX-L group and DEX-H group was significantly higher (P＜0.05).(2) The protein levels of Aβ-42 and p-tau-181 in cerebrospinal fluid of POCD group,DEX-L group and DEX-H group were significantly higher than those in sham-operated group (P＜0.05);the protein levels of Aβ-42 and p-tau-181 in cerebrospinal fluid of DEX-L group and DEX-H group were significantly lower as compared with those in POCD group (P＜0.05);DEX-H group had significantly lower protein levels of Aβ-42 and p-tau-181 in cerebrospinal fluid as compared with DEX-L group (P＜0.05).(3) The mRNA and protein expressions of mTOR,NF-κB p65 and TNF-α,Tau mRNA expression,and pS396 Tau protein expression in the hippocampus of the POCD group were significantly higher as compared with those in the sham-operated group (P＜0.05);the mRNA and protein expressions ofmTOR,NF-κB p65 and TNF-α,Tau mRNA expression,and pS396 tau protein expression in the hippocampus of the DEX-L group and DEX-H group were significantly lower as compared with those in the POCD group (P＜0.05);those in the DEX-H group were significantly lower than those in the DEX-L group (P＜0.05).Conclusion DEX can improve early POCD in mice,and the mechanism may be related to down-regulation of mTOR signaling pathway.
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Objective To investigate the effects of dexmedetomidine pre-treatment on pneumonocyte apoptosis and CCAAT/enhancer binding protein homologous protein (CHOP) in acute lung injury (ALI) induced by ischemia/reperfusion (I/R) during orthotopic liver transplantation in rats.Methods Forty adult male Sprague-Dawley (SD) rats were randomly divided into four groups by random number table method: sham operation group, I/R model group, dexmedetomidine low dose group and dexmedetomidine high dose group, 10 rats per group. Hepatic artery was ligated and cut off by two cuff method, and the portal vein was completely opened after donor liver transplanted into the recipient, thus, a hepatic I/R model was established. The perihepatic ligaments of rats were just separated after laparotomy in sham operation group and no other special treatment was performed. One hour prior to I/R, dexmedetomidine at a dose of 2.5μg·kg-1·h-1 and 5.0μg·kg-1·h-1, respectively, were pumped intravenously and finished within 1 hour in the rats of low dose group and high dose group. After experiment, the lung tissue was taken, and the lung wet/dry weight (W/D) ratio was determined. Pathological changes of lung tissue were observed and alveolar damage index of quantitative assessment (IQA) was tested by light microscope, and changes of ultrastructure of lung tissue were observed by transmission electron microscope. The mRNA and protein expressions of CHOP were detected respectively by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot. The apoptosis in lung tissue was determined by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) method and apoptosis index (AI) was calculated.Results Compared to sham operation group, the lung W/D ratio (4.94±0.84 vs. 2.29±0.54), IQA [(40.52±5.15)% vs. (4.55±1.85)%] and AI [(36.57±5.85)% vs. (2.85±0.95)%] in I/R model group were significantly higher (allP < 0.01); remarkable injury of lung tissue was confirmed by light microscope and transmission electron microscope in the I/R model group. Compared to I/R model group, the W/D ratio (3.29±0.85, 2.68±0.78 vs. 4.94±0.84), IQA [(23.69±2.62)%, (15.86±3.61)% vs. (40.52±5.15)%] and AI [(25.73±3.71)%, (14.66±2.61)% vs. (36.57±5.85)%] in dexmedetomidine low and high dose groups were markedly lower (allP < 0.01); under light and transmission electron microscopes, the injury of lung tissue in these two dose groups was notably alleviated. There was a large amount of apoptotic cells of pulmonary vascular endothelium and alveolar epithelium in I/R model group, while the cell apoptosis was distinctly decreased in dexmedetomidine low and high dose groups compared to that in model group. Compared to sham operation group, the expressions of CHOP mRNA [absorbance (A) value: 0.96±0.18 vs. 0.43±0.08] and protein (gray scale: 2.79±0.74 vs. 1.02±0.27) were significantly higher in I/R model group (bothP < 0.01). Compared to I/R model group, the expressions of CHOP mRNA (A value: 0.69±0.13, 0.56±0.12 vs. 0.96±0.18) and protein (gray scale: 1.96±0.58, 1.34±0.49 vs. 2.79±0.74) were significantly lower in dexmedetomidine low and high dose groups, the decrease in dexmedetomidine high dose group being more marked (allP < 0.01).Conclusion The pretreatment of dexmedetomidine can protect lung tissue against I/R injury during liver transplantation in rats, and the mechanism may be related to the suppression of CHOP activation and alleviation of lung tissue cell apoptosis.