扎里奴思方对局灶性脑缺血再灌注损伤大鼠P-糖蛋白的影响

摘要

目的：比较缺血损伤不同时段大鼠血脑屏障P－糖蛋白（ P－gp）时征表达及回药扎里奴思方对其表达的影响。方法 SD大鼠随机分为假手术组、模型组、尼莫地平组、扎里奴思方组，线栓法制备脑缺血再灌注模型，分别灌胃给药，于缺血再灌注后1、3、7、14 d取脑，检测大鼠脑皮质及海马区P－gp的表达。结果免疫组织化学染色结果显示，假手术组与模型组大鼠脑皮质及海马缺血区均可见 P－gp阳性染色。与假手术组比较，不同再灌注时间模型组P－gp表达量均有显著性差异（ P＜0．01），皮质及海马缺血区P－gp 表达量均升高；与模型组比较，扎里奴思方组及尼莫地平组大鼠脑皮质及海马区P－gp表达量明显降低，尤以扎里奴思方3、14 d组为明显（ P＜0．01 ） 。结论扎里奴思方发挥抗脑缺血损伤、神经元保护作用机制可能是通过调节血脑屏障上P－gp的双向表达而实现的。%Objective To research the P-glycoprotein( P-gp) expression on the blood-brain barrier at different times and the effect of Zhalinusi Fang after focal cerebral ischemia-reperfusion( I/R) in rats.Methods SD rats were divided randomly into sham-operated,mod-el,nimodipine and Zhalinusi Fang groups.Rat focal cerebral I/R model was established by middle cerebral artery occlusion with nylon thread.After rats were administered orally with corresponding drugs 1,3,7,14 d,the brain was taken out.Immunohistochemical method was used to detect P-gp expression in cerebral cortex and hippocampus.Results Immunohistochemical staining showed that in sham-operated and model groups, P-gp positive staining was visible at ischemic cerebral cortex and hippocampus region .Compared with that of sham-opera-ted group, P-gp expressions of different reperfusion time model groups were significant different(P<0.01),P-gp expression at ischemic cortex and hippocampus were increased.Compared with those of model group, of P-gp expression at cerebral cortex and hippocampus of ZLNSF and nimodipine groups were significantly decreased (P<0.01).Conclusions Zhalinusi Fang could promote the cerebral protection,its mecha-nism may be related to bidirectional regulation the expression of P-gp at blood-brain barrier.