补肾益气活血中药对大鼠缺血再灌注脑组织血管内皮生长因子表达和血脑屏障通透性的影响

摘要

目的 探讨脑缺血再灌注损伤后血管内皮生长因子(VEGF)的动态变化与血脑屏障(BBB)通透性改变的关系.方法 选择健康雄性Wistar大鼠80只随机分成3组,假手术组、生理盐水组和中药组,用线栓法建立短暂性局灶性脑缺血模型.采用伊文思蓝(Evans blue,EB)荧光测定法动态检测缺血再灌注1,3,7 d脑组织中EB含量的动态变化,采用VEGF免疫组织化学染色方法,在各再灌注时间点动态观察脑组织中VEGF表达.结果 模型组脑组织中EB含量与假手术组比较,差异有统计学意义(P < 0.05),呈现在缺血90 min再灌注24 h后迅速升高,72 h达到高峰,以后开始减少,至少持续到缺血再灌注7 d以上,中药组在各时间点均明显低于生理盐水组(P < 0.05),缺血90 min再灌注24 h半暗带,VEGF阳性细胞反应最明显,达峰值后迅速减少,中药在再灌注1～7 d对VEGF蛋白的表达没有影响(P > 0.05).结论 脑缺血再灌注后血脑屏障破坏和VEGF表达均呈现动态变化过程,但变化时程不一致,故VEGF不能介导血脑屏障破坏,未加重卒中后血管源性脑水肿的发生;补肾益气活血中药是通过改善血脑屏障的功能从而减轻血管源性脑水肿的.%Objective To inrestigate the relation between the flactuate change of VEGF and the transportation change of BBB after reperfusion of cerebral ischemia. Methods Eighty healthy-male Wistar rats were randomly assigned into three groups: sham-operated group, normal saline group and traditional Chinese medicine group. Facal and transient cerebral ischemia model was made by occluding the middle cerebral artery, and lynon line Evans blue fluorescence technique was used to detect the level of EB ischemia-reperfusion cerebral at 1, 3, 7 days. Immunohistochemistry was used to detect flactuatly expression of VEGF protein at each time points. Results The level of EB of the model group and sham-operated group significally increased in 24 hours, and reached the highest in 72 hours, then declined lasting at least 7 days after ischemia-reperfusior cerebral. The level of EB in traditional medicine group was abviausly lower than the normal saline group at each of the time points. The expression VEGF positive cells were must obvious, and decreased quickly after reaching the highest. The traditional Chinese medcine didn't affect expression VEGF protein in 1 to 7 days reperfusion. Conclusion These findings suggest both of BBB after ischemia-reperfusion cerebral and the expression VEGF are fluctuate change processes. But the change process isn't identical. So vasoactive cerebral edema is not made more serious by VEGF protein by BBB distraying. BuShen Yiqi Huoxue traditional Chinese medicine decreases vasoactive cerebral edema through improving the function of BBB.