脑缺血再灌注后大鼠皮质和纹状体微血管P-gp的表达变化

Expression change of P-gp in cortex and striatum capillary following cerebral ischemia reperfusion in rats

目的:观察P-糖蛋白(P-glycoprotein,P-gp)在局灶性脑缺血再灌注后大鼠脑内皮质及纹状体微血管的表达及其变化规律。方法:采用线栓法建立大鼠脑缺血再灌注模型,选取51只成年健康SD雄性大鼠,其中1只用于TTC染色,其余50只随机分为正常对照组(n=10)、假手术组(n=10)、脑缺血再灌注1 d、3 d和7 d组(n=10)。用免疫组织化学方法检测并计数各组P-gp在皮质和纹状体的微血管表达密度(micro vessel density,MVD)的变化;用Western Blot技术检测脑缺血后大脑皮层及纹状体微血管P-gp的表达变化。结果:脑缺血再灌注后皮质和纹状体的缺血侧微血管P-gp的MVD值和Western Blot检测结果均显示呈现增高的趋势,在3 d时达到高峰,皮质和纹状体分别与正常对照组及假手术组比较差异有统计学意义(P<0.01,P<0.05),7 d时回降至接近正常水平。皮质和纹状体的缺血侧及其对侧微血管P-gp的MVD值在脑缺血再灌注后均呈现增高的趋势,且均在3 d时达到高峰,但缺血侧比缺血对侧增高明显(P<0.05)。结论:脑缺血再灌注后大鼠皮质及纹状体微血管的P-gp表达均有不同程度的增高趋势,可能是脑组织的自我保护机制之一。

Objective： To observe the chaning pattern and the expression of P-glycoprotein（ P-gp） in reperfused ischemic cortex and striatum capillary in rats. Methods： Focal cerebral ischemia was induced by blocking middle cerebral artery using an intraluminal filament technique. 51 adult SD male rats were used for experiment. One rat was used for TTC staining to detect whether the focal cerebral ischemia is successful and the other rats were randomly divided into normal control group（ n = 10）,sham operated control group（ n = 10） and ischemia group including 1 d,3 d and 7 d after ischemia（ at each time point,n = 10）. The density of the P-gp immunnopositive microvessel（ MVD） in cortex and striatum was observed and counted. with immuhohisto-chemistry Meanwhile the expression change of P-gp in ischemic cerebral cortex and striatum capillary was analyzed by using Western Blot technique. Results： The results of positive MVD and Western Blot showed that the expression of P-gp in cortex and striatum of ischemia side after cerebral ischemic reperfusion exhibited an increasing trend. It the peaked at 3 d groups in cortex and striatum which compared with control groups and the difference was statistically significant（ P ﹤ 0. 01,P ﹤ 0. 05）,respectively,and then decreased toapproximately normal level at 7 d group. P-gp positive MVD showed a increasing trend in the ischemic side and its contralateral side of cortex and striatum after cerebral ischemic reperfusion. They all peaked significantly at 3 d,but the ischemia side was significantly higher than its contralateral side（ P ﹤ 0. 05）. Conclusion： The expression of P-gp in microvessels of cortex and striatum after cerebral ischemia reperfusion of rats shows different degrees of increasing tendency,which may be involved in the self-protection of the brain tissue.