异氟醚麻醉对严重感染脓毒症大鼠神经功能及相关信号通路的影响  

Effects of isoflurane anesthesia on neurological function and related signal pathways in rats with severe sepsis

作　　者：敖程斌 杨怡 AO Cheng-bin;YANG Yi(Yuhuan People′s Hospital,Taizhou,Zhejiang 317600,China;不详)

机构地区：[1]玉环市人民医院麻醉科,浙江台州317600 [2]台州市中心医院麻醉科,浙江台州318000

出　　处：《中华医院感染学杂志》2021年第20期3056-3060,共5页Chinese Journal of Nosocomiology

基　　金：浙江省自然科学基金资助项目(LQ17H080523)。

摘　　要：目的探究异氟醚麻醉对严重感染脓毒症大鼠神经功能及相关信号通路的影响。方法选取60只健康6周龄SD大鼠,采用盲肠结扎穿孔法制备大鼠脓毒症模型并随机分组法将大鼠分为:空白对照组(A组)、异氟醚组(B组)、p38丝裂原活化蛋白激酶(MAPK)信号通路抑制剂组(C组)和异氟醚+通路抑制剂组(D组),每组15只;A组吸入空气;B组吸入2%异氟醚维持麻醉2 h,侧脑室注射生理盐水5μl;C组侧脑室注射p38 MAPK抑制剂5μl;D组侧脑室注射p38 MAPK抑制剂5μl并吸入2%异氟醚维持麻醉2 h;采用Longa法评价大鼠神经功能损伤,Y-迷宫实验检测大鼠脑认知功能;采用细胞流式法检测各组大鼠海马CA1区神经细胞凋亡情况;采用蛋白质印记检测大鼠海马组织凋亡相关蛋白Bax,Bcl-2,Caspase-3相对表达情况;采用蛋白质印迹检测p38 MAPK信号通路相关蛋白相对表达情况。结果异氟醚组和异氟醚+通路抑制剂组大鼠逃离时间、错误反应次数、神经功能评分、海马区神经细胞凋亡率、Bax,Caspase-3,p-p38和p-核因子-κB(NF-κB)蛋白相对表达高于空白对照组(P<0.05),Bcl-2蛋白相对表达水平降低(P<0.05);p38 MAPK信号通路抑制剂组和异氟醚+通路抑制剂组大鼠逃离时间、错误反应次数、神经功能评分、海马区神经细胞凋亡率、Bax,Caspase-3,p-p38和p-NF-κB蛋白相对表达水平均低于异氟醚组(P<0.05),Bcl-2蛋白相对表达水平升高(P<0.05)。结论异氟醚麻醉会诱导严重感染脓毒症大鼠海马区神经细胞凋亡并损伤大鼠神经功能,其作用机制与激活p38 MAPK信号通路相关。OBJECTIVE To explore the effect of isoflurane anesthesia on neurological function and related signal pathway in rats with severe sepsis.METHODS Sixty healthy adult SD rats were selected to establish the sepsis model by cecal ligation and perforation,and the rats were randomly divided into blank control group(group A),isoflurane group(group B),p38 MAPK signaling pathway inhibitor group(group C) and isoflurane+pathway inhibitor group(group D),with 15 rats in each group.Rats in group A were inhaled with air,rats in group B were inhaled with 2% isoflurane to maintain anesthesia for 2 h,and were injected with 5 μL normal saline into lateral ventricle,rats in Group C were injected with 5μL p38 MAPK inhibitor into lateral ventricle,and rats in group D were injected with 5 μl of p38 MAPK inhibitor into lateral ventricle and inhaled with 2% isoflurane to maintain anesthesia for 2 hours.Longa method was used to evaluate the neurological deficits of rats,and Y-maze test was used to detect the cognitive function of rats.The flow cytometry was used to detect the apoptosis of nerve cells in hippocampal CA1 area of rats in each group.Western blot assay was used to determine the relative expression of Bax,Bcl-2 and Caspase-3 proteins in hippocampus of rats.Western blot assay was used to detect the relative expression of p38 MAPK signaling pathway related proteins.RESULTS The escape time,error reaction times,neurological function score,apoptosis rate of hippocampal neurons,relative expression levels of Bax,Caspase-3,p-p38 and p-NF-κB protein in isoflurane group and isoflurane+pathway inhibitor group were all significantly higher than those of the blank control group(P<0.05),while the relative expression level of Bcl-2 protein was decreased significantly(P<0.05).The escape time,error reaction times,neurological function score,apoptosis rate of hippocampal neurons,relative expression levels of Bax,Caspase-3,p-p38 and p-NF-κB protein in p38 MAPK signaling pathway inhibitor group and isoflurane+pathway inhibitor group were all s

关 键 词：异氟醚 麻醉 神经功能 细胞凋亡 

分 类 号：R459.7[医药卫生—急诊医学]