二氮嗪对大鼠脑缺血再灌注损伤的保护作用及其机制

Protective effect of diazoxide on the cerebral ischemia reperfusion injury in rats and its mechanism

目的研究二氮嗪开放线粒体ATP敏感性钾通道(MitoKATP)对大鼠脑缺血再灌注(I/R)损伤的作用及其机制。方法采用线栓法建立大鼠局灶脑I/R损伤模型,将30只大鼠随机分成三组(假手术组、缺血组、缺血+二氮嗪治疗组),观察各组脑梗死体积和线粒体标志酶活性、凋亡细胞数变化。结果与缺血组比较,治疗组脑梗死体积明显减少〔(10782±2037)m3vs(28517±3429)m3〕,线粒体标酶活性明显增高〔SDH(3212±363)vs(2224±387),CO(208±27)vs(1332±247)〕,凋亡细胞数明显减少(12232±1156vs8704±1116)(P<001)。结论二氮嗪对大鼠I/R损伤具有保护作用,其机制与开放MitoKATP通道、维护线粒体功能、抑制细胞凋亡有关。

Objective To investigate the effect and its mechanism of diazoxide on cerebral ischemia/reperfusion (I/R) by opening mitochondrial ATP-sensitive K+ channel (mitoK_~ATP ). Methods The I/R models of rats were performed by thread embolism of middle cerebral artery for 2 and 22 h of reperfusion. 30 rats were randomly divided into three groups: sham-operated group, ischemia group and diazoxide treatment group. The cerebral infarction size (IS), activity of succinate dehydrogenase (SDH) and cytochrome oxidase (CO), the change of apoptosis cells were observed in the above groups respectively. Results Compared with ischemia group, IS was decreased, the activity of SDH and CD was increased, the apoptosis cells were decreased significantly 〔(107.82±20.37)mm3 vs.(285.17±34.29)mm3, 32.12±3.63 vs. 22.24±3.87, 20.8±2.7 vs. 13.32±2.47, P<0.01, respectively〕. Conclusions Diazoxide can protect rat against cerebral I/R injury through opening mitoK_~ATP , preserving the function of the mitochondria and inhibiting neuron apoptosis.