丙泊酚对大鼠脑缺血-再灌注损伤时含Kir6.2和SUR1亚基的线粒体ATP敏感性钾通道的影响

Effects of propofol on the mitochondria ATP-sensitive potassium channel that contains Kir6.2 and SUR1 subunits in rats with cerebral ischemia-reperfusion injury

目的评价丙泊酚对大鼠脑缺血-再灌注损伤时含Kir6.2和SUR1亚基的线粒体ATP敏感性钾通道（mitoKATP通道）的影响。方法选择SD雄性大鼠24只,3.0-3.5月龄,体重280-320g,采用随机数字表法,将其均分为三组：假手术组（S组）、缺血-再灌注组（IR组）、丙泊酚组（P组）。P组于股静脉注射丙泊酚50mg/kg,S组、IR组注射等容量生理盐水。随后,IR组、P组采用线栓法建立局灶性大鼠脑缺血-再灌注损伤模型,缺血2h,再灌注24h。于再灌注24h时行神经功能缺陷评分,采用TTC法测定脑梗死体积;采用RT-PCR法和Western blot法检测mitoKATP通道Kir6.2和SUR1亚基mRNA和蛋白的表达水平。结果与S组比较,IR组和P组神经功能缺陷评分明显升高,脑梗死体积百分比明显增大,IR组mitoKATP通道Kir6.2亚基mRNA和蛋白的表达明显下调（P〈0.05）;与IR组比较,P组神经功能缺陷评分明显降低、脑梗死体积百分比明显减小,mitoKATP通道Kir6.2亚基mRNA和蛋白的表达上调（P〈0.05）;三组间mitoKATP通道SUR1亚基mRNA和蛋白的表达水平差异无统计学意义。结论丙泊酚减轻大鼠脑缺血-再灌注损伤的机制与上调KATP通道Kir6.2亚基的表达有关。

Objective To evaluate the effects of propofol on the mitochondria ATP-sensitive potassium channel that contains Kir6.2and SUR1 subunits in rats with cerebral ischemia-reperfusion injury.Methods Twenty-four male Sprague-Dawley rats,weighing 280-320 g,were randomly divided into 3groups（n=8）：sham operation group（group S）,cerebral ischemia-reperfusion group（group IR）and propofol group（group P）.Transient focal cerebral ischaemia and reperfusion injury was induced by middle cerebral artery occlusion model in group P and group IR.Rats in group P were injected 50mg/kg propofol 2hr prior to ischemia.In groups S and IR,1ml of normal saline was injected instead.The neurological scores were evaluated and brain infarction size was measured using TTCstaining.The mRNA expression levels of Kir6.2and SUR1 were analyzed by quantitative polymerase chain reaction,while the protein levels of Kir6.2and SUR1 were determined by western blot analysis.Results Compared with group S,neurological scores and infarction size was increased in group IR and group P,and the mRNA and protein levels of Kir6.2in the group IR were down-regulated（P〈0.05）.Compared with group IR,neurological scores and infarction size decreased and the mRNA and protein levels of Kir6.2were up-regulated in group P（P〈0.05）;the expressions of SUR1 in the three groups showed no significant difference.Conclusion Propofol could attenuate cerebral ischemia and reperfusion injury through up-regulating Kir6.2expression in rats.