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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 investigate the expression of P-glycoprotein (P-gp) in cerebral blood vessels and cells after cerebral ischemia and to explore the relationship between P-gp and cerebral ischemia. Methods: The middle cerebral artery occlusion (MCAO) model of rats was established by minimally invasive craniotomy. Thirty rats were randomly divided into 3 ischemic groups at 1, 2 and 3 days after ischemia, and normal control group and sham operation Group (n = 6). The anti-P-gp antibody was used to detect the expression of P-gp in the vascular wall and brain cells, and the expression changes at different time points after ischemia. Results: In the ischemic and necrotic areas, a large number of P-gp-positive cells were found in the ischemic and necrotic areas and peaked at 3 days after ischemia. Only a small amount of P-gp was expressed in the ischemic area, P-gp was abundantly expressed on the vascular wall in the cortex and striatum of the area, and significantly increased with the prolongation of ischemia, reaching its peak in the 3 d group. Conclusions: The large amount of P-gp expression in the blood vessel wall and cells in the rat brain after cerebral ischemia suggests that the synthesis of multidrug-resistant protein increases after brain injury, and at the same time it also affects the entry of clinical drugs.