阿司匹林对脑缺血-再灌注损伤大鼠神经保护作用的机制

The mechanism of neuroprotective effect of aspirin after cerebral ischemia/reperfusion injury in rats

目的探讨阿司匹林对脑缺血-再灌注损伤大鼠神经保护作用的机制。方法采用线栓法建立大鼠大脑中动脉缺血-再灌注模型。将48只W istar大鼠分为对照组(A组)和小剂量组(B组,阿司匹林20 mg/kg)、中等剂量组(C组,阿司匹林80 mg/kg)、大剂量组(D组,阿司匹林320 mg/kg),每组12只。实验组于脑缺血-再灌注术后连续3 d腹腔注射相应剂量的阿司匹林。脑缺血-再灌注后当日始连续4 d对每组动物进行Bederson评分并记录。第4天处死各组大鼠,用2,3,5-三苯基氯化四氮唑(TTC)染色法测定梗死灶体积,用缺口末端标记(TUNEL)技术原位标记凋亡细胞,用免疫组化法检测凋亡调节基因相关蛋白BCL-2和BAX的表达。结果用阿司匹林干预后,B、C、D组大鼠肢体功能改善,与A组相比,神经功能缺损评分明显降低,梗死体积显著缩小(分别较A组缩小16.3%、19.2%和12.8%);缺血周边区凋亡细胞阳性率A组为58%,B组为37%,C组为35%,D组为40%;缺血区BCL-2蛋白表达A组为38%,B组为55%,C组为60%,D组为50%;BAX蛋白表达A组为50%,B组为34%,C组为33%,D组为42%。三个药物组间进行比较,小、中等剂量阿司匹林组对脑梗死的疗效优于大剂量组。结论早期应用阿司匹林可减轻大鼠脑缺血-再灌注后的神经功能缺损,具有神经保护作用。

Objective To explore the mechanism of neuroprotective effects of aspirin after cerebral ischemia/reperfusion injury in rats. Methods Cerebral ischemia/reperfusion model of middle cerebral artery occlusion was established in rats using the suture method. Forty-eight experimental rats were divided into control group （group A）, low-dose group （group B; aspirin 20 mg/kg）, moderate-dose group （Group C; aspirin 80 mg/kg）, and high-dose group （group D; aspirin 320 mg/kg）, each group had 12 rats. Aspirin were continuously injected intraperitoneally in the rats in experimental groups for 3 days as an interference factor after cerebral ischemia/reperfusion. At the same day after cerebral ischemia/reperfusion, the neurological function of all the rats in each group was evaluated for 4 days by the Bederson score and was documented. All the rats in each group were killed at day 4. Cerebral infarct volume were measured by TYC stain, the apeptosis in situ labeling were detected by TUNEL, and the expressions of apoptosis-regulating proteins BCL-2 and BAX were detected by immunohistochemistry. Results Limb function improved in the groups of A, B, and C after aspirin intervention. As compared with the group A, the neurological deficit scores decreased significantly, and the infarct volume reduced significantly （compared with the group A, the infarct volume decreased 16. 3%, 19. 2%, and 12. 8%, respectively） ; the positive rate of apoptosis cells in the surrounding iscbemic areas decreased, they were 58%, 37%, 35%, and 40% in groups A, B, C, and D; the protein Bcl-2 expression in the ischemic areas increased 38%, 55%, 60% , and 50% in groups A, B, C, and D; and protein Bax expression decreased 50%, 34%, 33%, and 42% in groups A, B, C, and D. Among the 3 treatment groups, the efficacy of the low-and moderate-dose groups was better than that of the high-dose group. Conclusion Early use of aspirin may decrease neurological deficits after cerebral ischemia/reperfusion in rats, and thus exert its neuroprotective effect.