激动GHB受体对大鼠局灶性脑缺血再灌注损伤的保护作用及机制探讨

摘要

目的 观察激动γ-羟基丁酸(GHB)受体对大鼠局灶性脑缺血再灌注损伤的保护作用,并探讨其机制.方法 成年清洁级雄性SD大鼠,体质量(250±20)g,随机分为5组,假手术组(sham组)、缺血再灌注组(I/R组)及NCS-356(GHB受体选择性激动剂)160、320、640 μg/kg剂量组,采用改良的Longa线栓法建立大鼠局灶性脑缺血再灌注模型,分别进行损伤大鼠神经功能评分(5分制评分法),Western blot法检测Gi蛋白.结果 与模型组比较,640 μg/kg NCS-356组能降低神经功能评分(P＜0.05),同时320、640 μg/kg NCS-356剂量组能升高大鼠脑缺血皮层神经元细胞内Gi蛋白(P＜0.05)水平.结论 激动GHB受体对大鼠局灶性脑缺血再灌注损伤具有一定的保护作用,其机制可能与升高Gi蛋白水平有关.%Objective To investigate the change of Gi in the protection effect of agitating gamma-hydroxybutyric acid (GHB) receptor on focal cerebral ischemia-reperfusion injury in rats. Methods The ripe male Sprague-Dawley rats weighing 240-280 g were randomly divided into five groups; sham operation group (sham) , ischemia-reperfusion group (I/R) , and NCS-356 160, 320, 640 μg/kg groups. These groups were administered NCS-356 in right lateral cerebral ventricle. The middle cerebral artery occlusion (MCAO) model referring to Longa's method with modifications was adopted. The effect of GHB receptor on behavioral consequence of MCAO rats was studied 2 h after ischemia reperfusion. After 24 h of ischemia reperfusion, part animals' ischemic cortex was used to measure the content of Gi by Western blot. Results The neurological function score in NCS-356 640 μg/kg group was obviously lower than that in I/R group ( P < 0.05). The level of Gi in NCS-356 320 and 640 μg/kg groups were higher compared with I/R group ( P < 0.05 ). Conclusions Activating GHBR has protective effects on ischemic brain injury. The neuroprotective effect is related with the increase content of Gi in MCAO rats.