右美托咪定辅助氯胺酮麻醉对大鼠海马区神经细胞的保护作用

发布时间：2018-04-19 03:06

本文选题：麻醉 + 右美托咪定　；参考：《山东医药》2017年28期

【摘要】：目的探讨右美托咪定辅助氯胺酮麻醉对大鼠海马区神经细胞的保护作用。方法将32只SD大鼠按照随机数字表法分为空白对照组、氯胺酮组、右美托咪定组和联合用药组,每组8只。空白对照组腹腔注射生理盐水50 m L/kg,间隔5 min皮下注射生理盐水50 m L/kg;氯胺酮组腹腔注射氯胺酮70 mg/kg,间隔5 min皮下注射生理盐水50 m L/kg;右美托咪定组腹腔注射右美托咪定25μg/kg,间隔5 min皮下注射生理盐水50 m L/kg;联合用药组腹腔注射氯胺酮70 mg/kg,间隔5 min皮下注射右美托咪定25μg/kg;各组均每天注射1次,连续注射3天。各组随机取4只,检测首次注射即刻(t0)及末次注射15、30、45、60、75、90 min(t1~t6)呼吸频率、翻正反射消失时间、翻正反射消失持续时间以及夹尾反射完全消失时间,Morris水迷宫实验检测各组训练1~5天的逃避潜伏期。各组剩余大鼠末次注射结束,断头处死,TUNEL法检测海马区神经细胞凋亡率,Western blotting法检测PKC、ERK1/2、Bcl-2蛋白表达。结果与联合用药组比较,氯胺酮组翻正反射消失时间明显延长,镇静维持时间、翻正反射消失持续时间明显缩短,两组比较P均0.05。t1、t2、t3时,氯胺酮组呼吸频率均显著高于空白对照组、右美托咪定组和联合用药组同时间(P均0.05)。空白对照组、右美托咪定组、联合用药组各时间逃避潜伏期比较P均0.05;训练第4、5天,氯胺酮组逃避潜伏期较空白对照组、右美托咪定组和联合用药组明显延长(P均0.05)。氯胺酮组神经细胞凋亡率明显高于空白对照组、右美托咪定组和联合用药组(P均0.05),而空白对照组、右美托咪定组和联合用药组神经细胞凋亡率比较P均0.05。氯胺酮组海马区PKC、ERK1/2、Bcl-2蛋白表达明显低于空白对照组、右美托咪定组和联合用药组(P均0.05),而空白对照组、右美托咪定组和联合用药组海马区PKC、ERK1/2、Bcl-2蛋白表达比较P均0.05。结论右美托咪定辅助氯胺酮麻醉对大鼠海马区神经细胞凋亡具有保护作用,其作用机制可能与激活PKC-ERK1/2-Bcl-2信号通路有关。
[Abstract]:Objective to investigate the protective effect of dexmetomidine-assisted ketamine anesthesia on hippocampal neurons in rats.Methods Thirty-two Sprague-Dawley rats were randomly divided into control group, ketamine group, dexmetomidine group and combined treatment group with 8 rats in each group.The blank control group received intraperitoneal injection of normal saline 50 mL / kg at intervals of 5 min; ketamine group received 70 mg / kg ketamine intraperitoneally and saline 50 mL / kg at intervals of 5 min; dextromidine group received right intraperitoneal injection of normal saline 50 mL / kg; Ketamine group received intraperitoneal injection of normal saline 50 mL / kg; ketamine group received intraperitoneal injection of ketamine 70 mg / kg; interval of 5 minMetoimidine 25 渭 g / kg was subcutaneously injected with normal saline 50 mL / kg at intervals of 5 min, ketamine 70 mg / kg was injected intraperitoneally in the combined treatment group and dexmetidine was injected subcutaneously at intervals of 5 min.Continuous injection for 3 days.Four rats in each group were randomly selected. The respiratory frequency and the time of disappearance of righting reflex were measured in the first injection (n = 4) and the last injection (n = 15 30) (n = 45) and 90 min / t ~ (-1) t ~ (6), respectively.The time of disappearance of righting reflex and complete disappearance of tail reflex was measured by Morris water maze test. The escape latency of 1 to 5 days training in each group was measured.At the end of the last injection of the remaining rats in each group, the apoptotic rate of hippocampal neurons was detected by Tunel method and the expression of Bcl-2 protein was detected by Western blotting.Results compared with the combined treatment group, the vanishing time of the righting reflex in the ketamine group was significantly prolonged, the time of sedation maintenance and the duration of the vanish of the righting reflex were significantly shortened, compared with that in the ketamine group (P < 0.01).The respiratory frequency of ketamine group was significantly higher than that of blank control group.The escape latency of control group, dexmetidine group and combined treatment group was 0.05, and the escape latency of ketamine group was significantly longer than that of blank control group, dexmetomidine group and combined treatment group were significantly longer than that of control group on the 4th day of training (P 0.05).The apoptotic rate of nerve cells in ketamine group was significantly higher than that in blank control group (P 0.05) in dexmetomidine group and combination treatment group, while in blank control group, dexmetomidine group and combined treatment group (P 0.05).The expression of Bcl-2 protein in the hippocampal area of ketamine group was significantly lower than that in the control group. The expression of Bcl-2 protein was significantly lower in the dexmetomidine group and combined treatment group than in the blank control group, the dexmetomidine group and the combined treatment group (P < 0.05), while the expression of Bcl-2 protein in the hippocampal area of the control group, the dexmetomidine group and the combined treatment group was significantly lower than that in the control group (P < 0.05).Conclusion dexmetomidine-assisted ketamine anesthesia has protective effect on neuronal apoptosis in rat hippocampal area, and its mechanism may be related to activation of PKC-ERK1/2-Bcl-2 signaling pathway.
【作者单位】：山东省医学科学院附属医院;山东省立医院;
【基金】：山东省医药卫生科技发展计划(2016WSB01061)
【分类号】：R614

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