电针预处理对脑缺血再灌注大鼠皮层内质网IRE1-XBP1信号通路的影响

Effect of electroacupuncture preconditioning on IRE1-XBP1 signaling pathway in endoplasmic retic-ulum in cortex in a rat model of cerebral ischemia-reperfusion

目的评价电针预处理对脑缺血再灌注大鼠皮层内质网肌醇酶1-x盒连接蛋白1（IREl-XBPl）信号通路的影响。方法清洁级健康雄性sD大鼠108只，8-12周龄，体重200-250g，采用随机数字表法分为3组（n=36）：假手术组（s组）、脑缺血再灌注组（I／R组）和电针预处理组（EA组）。采用线栓阻断右侧大脑中动脉2h后恢复灌注的方法制备大鼠局灶性脑缺血再灌注损伤模型。EA组于缺血前5d开始接受电针刺激百会穴30min，1次／d，连续5d，最后1次预处理后24h制备模型。于再灌注6、12和24h时神经功能缺损评分后处死大鼠取大脑皮层缺血区，透射电镜下观察细胞的超微结构，采用Westernblot法检测IREl和XBPl的表达水平。结果与s组比较，I／R组和EA组各时点神经功能缺损评分升高，皮层缺血区IREl和XBPl表达上调（P〈0．01）：与I／R组比较，EA组各时点神经功能缺损评分降低，皮层缺血区IREl和XBPl表达上调（P〈0．05）。EA组皮层缺血区细胞损伤较I／R组减轻。结论电针预处理减轻大鼠脑缺血再灌注损伤的机制与进一步激活IREl-XBPl信号通路，缓解内质网应激有关。

Objective To evaluate the effect of electroacupuncture （EA） preconditioning on inosi-tol-requiring kinase 1 （IRE1）-X-box binding protein 1 （XBP1） signaling pathway in endoplasmic reticulum in the cortex in a rat model of cerebral ischemia-reperfusion （I/R）. Methods One hundred and eight pathogen-free healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-250 g, were assigned into 3 groups （n= 36 each） using a random number table： sham operation group （group S）, group I/R and EA preconditioning group （group EA）. Focal cerebral I/R was induced by occlusion of right middle cere-bral arteries for 2 h followed by reperfusion in rats anesthetized with chloral hydrate. In group EA, Baihui acupoints were stimulated with an electric stimulator for 30 min once a day for 5 consecutive days starting from 5 days before ischemia, and the model was established at 24 h after the last preconditioning. Rats were sacrificed after neurological deficit was scored at 6, 12 and 24 h of reperfusion, brains were removed, and the ischemic area in cerebral cortex was isolated for examination of the cell uhrastructure (with an elec-tronic microscope） and for determination of the expression of IRE1 and XBP1 （by Western blot）. Results Compared with group S, the neurological deficit scores were significantly increased, and the expression of IRE1 and XBP1 in the ischemic area was up-regulated at each time point in I/R and EA groups (P〈 0. O1). Compared with group I/R, the neurological deficit scores were significantly decreased, and the ex-pression of IRE1 and XBP1 was up-regulated at each time point in group EA （P〈0. 05）. The cell damage in the ischemic area in cerebral cortex was significantly attenuated in group EA when compared with group I/ R. Conclusion The mechanism by which EA preconditioning attenuates cerebral I/R injury is related to activating IRE1-XBP1 signaling pathway and relieving endoplasmic reticulum stress in rats.