mito-KATP通道在异氟醚预处理减轻沙土鼠脑缺血-再灌注损伤中的作用

摘要

目的 观察mito-KATP通道在异氟醚(ISO)预处理脑保护中的作用.方法 健康沙土鼠60只随机均分为六组:对照组(A组)、缺血-再灌注组(B组)、1.5％ISO预处理组(C组)、1.5％ISO预处理+5-羟葵酸(5-HD)5 mg/kg组(D组)、1.5％ISO预处理+5-HD 10 mg/kg组(E组)、1.50％ ISO预处理+5-HD 15 mg/kg组(F组).预处理方法为连续5d吸入1.5％ ISO1 h/d;末次预处理24 h后行缺血-再灌注,D、E、F组缺血前30 min分别腹腔注射5、10、15 mg/kg 5-HD.48 h后HE染色观察脑组织形态学变化,TUNEL法检测海马神经元凋亡,免疫组化检测Bd-2及Bax在海马神经元的表达.结果 与A组比较,B、C、D、E、F组脑损伤评分、神经细胞凋亡率、Bax表达均明显升高(P＜0.05)；而C、D、E、F组Bcl-2阳性表达明显升高(P＜0.05).与C组比较,E、F组脑损伤评分、神经细胞凋亡率及Bax表达明显升高(P＜0.05),而Bcl-2阳性表达降低(P＜0.05).结论 mito-KATP通道在ISO预处理脑保护效应中起重要作用.%Objective To investigate the effect of mito-KATP channel in isoflurane preconditioning induced brain protection in gerbils. Methods Sixty healthy Mongolian gerbils were randomly divided into 6 groups: group A was normal control; group B was the reperfusion; group C was 1. 5% isofulurance preconditioning; group D was 1.5% isofulurance preconditioning+5-HD 5 mg/kg; group E was 1.5% isofulurance preconditioning + 5-HD 10 mg/kg; group F was 1.5% isofulurance preconditioning +5-HD 15 mg/kg group. Once daily of 1. 5% isoflurane was given for five days. Ischemia-reperfusion injury was occurred 24 h after the last preconditioning day. Groups of D, E and F were injected with 5-HD 5, 10, 15 mg/kg 30 min before ischemia-reperfusion injury. HE staining was used to observe the injury of cerebrum, and the expressions of Bcl-2 and Bax were detected with immunohistochemistry, and TUNEL was used to analyze the neuronal apoptosis. Results Compared with group A, other five groups displayed an improvement in cerebral injury, neuronal apoptosis and Bax expression (P<0. 05), but groups C, D, E, F had a higher positive expression of Bcl-2 (P<0. 05). When compared with group C, groups E and F had higher scorings in cerebral injury, neuronal apoptosis and Bax expression (P<0. 05), but the positive Bcl-2 was decreased (P<0.05). Conclusion The mito-KATP channel plays an important role in brain protection induced by isoflurance preconditioning.