P-糖蛋白在永久性脑缺血大鼠脑内的表达

目的:研究脑缺血后多药耐药蛋白(P-glycoprotein,P-gp)在脑内血管及细胞中的表达变化,探讨P-gp与脑缺血的关系。方法:应用微创开颅法建立大鼠大脑中动脉闭塞(MCAO)模型,30只大鼠随机分为缺血后1、2、3 d共3个缺血组,以及正常对照组和假手术组(n=6)。用抗P-gp抗体进行免疫组化染色观测血管壁及脑内细胞是否表达P-gp以及缺血后不同时间点的表达变化。结果:缺血后1、2、3 d组中,在缺血坏死区可见大量表达P-gp的阳性细胞,3 d时达高峰;缺血区仅有少量血管表达P-gp,在缺血区周围皮质及纹状体中血管壁上大量表达P-gp,并随缺血时间的延长而显著增多,在3 d组达高峰。结论:脑缺血后大鼠脑内血管壁及细胞中大量表达P-gp,提示脑内受损后多药耐药蛋白合成增加,在自我保护的同时也影响了临床药物的进入。

Expression of P-glycoprotein in permanent cerebral ischemia in adult rats

Objective: To explore the expression of P-glycoprotein(P-gp)in the brain capillary and cells after cerebral ischemia.Methods: The rat model of middle cerebral artery occlusion(MCAO) was established by minimal in vasivecraniotomy.Thirty adult male SD rats were randomly divided into ischemia group including 1 day,2 days,3 days after ischemia(at each timepoint,n=6);sham operation group(n=6) and normal control group(n=6).The expression change of P-gp immunoreactivity was observed in capilary and cells and each timepoint following MCAO by immunohistochemistry.Results: The P-gp-immunoreactivity was expressed in the cells of infarct region,observed in capillary endothelium of cortex and striatum around the ischemic region at 1 day,2 days,and 3rd day,especially at 3rd day after MCAO.Conclusion: Over expression of P-gp in cerebral cells and capillary suggest that brain synthesizes much more multidrug resistance protein after injury.It might facilitate neuroprotection and inhibit the therapeutic effect of medical drag.