摘要
目的观察ATP敏感性钾通道(KATP)开放剂尼可地尔(nicorandil)对大鼠脑缺血/再灌注(I/R)损伤的保护作用及其机制。方法将60只雄性Wistar大鼠随机分为4组:A组(假手术组)、B组(脑缺血再灌注组)、C组(脑缺血再灌注+尼可地尔组)及D组(脑缺血再灌注+尼可地尔+5-HD组),采用线栓法建立大鼠大脑中动脉闭塞(MCAO)模型,各组于脑缺血2h后进行再灌注,再灌注22h后观察各组大鼠神经功能评分、脑梗死体积、线粒体标志酶活性和脂质过氧化降解产物丙二醛(malondialdehyde,MDA)的含量。结果(1)B、C、D组再灌注22h后神经功能评分显著低于A组,脑梗死体积、脂质过氧化物MDA含量均显著高于A组,线粒体标志酶活性SDH、CO表达显著低于A组(P<0.01);(2)与B、D组比较,C组神经功能评分明显升高,脑梗死体积、MDA含量明显减少,SDH、CO活性明显增高(P<0.01);(3)B组和D组各指标之间比较差异均无显著性(P>0.05)。结论尼可地尔对大鼠脑缺血再灌注损伤具有保护作用,其机制可能与开放mitoKATP通道、维护线粒体功能、减少氧自由基产生有关。
Objective To investigate the effect and its mechanism of nicorandil, a mitochondrial ATP- sensitive K＋ channel opener, on cerebral ischemia/reperfusion（I/R）. Methods The I/R models of rats were performed by thread embolism of middle cerebral artery for 2 h of reperfusion. After 22 h of reperfusion, 60 rats were randomly divided into four groups： sham-operated group, ischemia group, nicorandil treatment group and 5-HD-nicorandil group. Neuropsychological score, infarct volume by total brain slices calculation, activity of succinate ehydrogenase （SDH） and cytochrome oxidase（CO）, and content of malondialdehyde （MDA） were observed in the above groups respectively. Results Compared with ischemia group and 5-HD- nicorandil group, improved neuropsychological score, decreased infarct volume and content of malondialdehyde （MDA）, increased the activity for SDH and CD were all in nicorandil treatment group. Conclusions Nicoran dil can prevent rat from cerebral I/R injury by opening mitOKAwP, preserving the function of the mitochondria and decreasing reactive oxygen species generation.
出处
《卒中与神经疾病》
2008年第4期217-220,共4页
Stroke and Nervous Diseases
基金
山东省科技攻关计划项目(编号为2006GG3202004)
关键词
线粒体ATP敏感性钾通道
脑缺血/再灌注损伤
氧自由基
Mitochondrial ATP-sensitive K＋ channel. （mitoKATP） Cerebral ischemia/reperfusion injury Free radicals
