P-糖蛋白在永久性脑缺血大鼠脑内的表达

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

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。

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 iscbemia 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.