脑血疏口服液对脑出血模型大鼠脑组织ZO-1和AQP4表达的影响

王晓峰　田超　张岩　袁梦晨　张涵莱　王丽琴　安娜　高永红

[摘要] 目的 觀察脑血疏口服液对大鼠脑出血模型脑组织血脑屏障紧密连接蛋白1（ZO-1）、水通道蛋白4（AQP4）表达的影响。 方法 采用尾状核注射胶原蛋白酶Ⅶ建立脑出血模型。采用随机数字表法将8周龄SPF级健康雄性SD大鼠分为假手术组、模型组、脑血疏组，每组8只。脑血疏组按照0.27 mL/（100 g·d）进行灌胃给药，假手术组及模型组分别给予等量生理盐水。造模后7 d，HE染色法观察大鼠血肿周围组织病理形态学改变，透射电镜法观察超微结构。Western blot检测各组血肿周围脑组织ZO-1、AQP4的表达变化。 结果 与假手术组比较，脑出血7 d模型组HE染色出血灶大片坏死，血肿周围细胞肿胀变性，核结构不清晰;透射电镜中可见脑血管与周围组织间隙增宽，且星形胶质细胞足突水肿明显;模型组大鼠脑组织中ZO-1蛋白表达量降低，AQP4蛋白表达量增加（P < 0.05）。与模型组比较，脑血疏组病理形态结构明显改善，ZO-1蛋白表达量明显升高，AQP4蛋白表达量显著降低（P < 0.05）。 结论 脑血疏口服液能够有效促进大鼠脑出血后ZO-1蛋白的表达，抑制AQP4蛋白的表达，降低血脑屏障的通透性，减轻脑水肿，对脑出血后脑组织发挥保护作用。

[关键词] 脑血疏口服液;脑出血;紧密连接蛋白1;水通道蛋白4

[中图分类号] R743.34          [文献标识码] A          [文章编号] 1673-7210（2019）06（a）-0008-05

Effect of Naoxueshu Oral Liquid on the expression of ZO-1 and AQP4 proteins in rat model of intracerebral hemorrhage

WANG Xiaofeng1   TIAN Chao1   ZHANG Yan2   YUAN Mengchen1   ZHANG Hanlai1   WANG Liqin1   AN Na1   GAO Yonghong1

1.Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing， Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine， Beijing   100700， China; 2.Department of Neurosurgery， the Seventh Medical Center of Chinese People′s Liberation Army General Hospital， Beijing   100700， China

[Abstract] Objective To observe the effect of Naoxueshu Oral Liquid on the expression of zonula occludens 1 （ZO-1）， aquaporin-4 （AQP4） in brain of model rats with intracerebral hemorrhage. Methods A model of intracerebral hemorrhage was produced by injection of collagenase Ⅶ into the caudatum of rats. Healthy male SD rats of SPF grade （8 weeks） were divided into three groups by random number table： the sham group， the model group and the Naoxueshu group， with 8 rats in each group. Naoxueshu Oral Liquid was administrated intragastrically by 0.27 mL/（100 g·d）， while saline was administrated to the sham group and model group by the same way. The histopathological change of brain tissue was tested by HE staining and transmission electron microscopy on the 7 d after intracerebral hemorrhage. The expression of ZO-1 and AQP4 in perihematoma tissue was detected by Western blot. Results Compared with the sham group， HE staining showed that large necrosis in perihematomal and the cells were irregular， loose， swollen， and the nuclear structure was unclear and undistinguishable in the 7-day model group. Transmission electron microscopy revealed that the gap between cerebral blood vessels and surrounding tissues was widened， and vacuolar changes were observed， and the astrocyte podocyte edema was obvious. The expression of ZO-1 protein in the brain tissue of the 7-day model group was decreased and AQP4 protein was increased （P < 0.05）. Compared with the model group， the pathological structure of the cerebral blood group was significantly improved， and the expression of ZO-1 protein was significantly increased， while the expression of AQP4 protein was significantly decreased （P < 0.05）. Conclusion Naoxueshu Oral Liquid can effectively increase the expression of ZO-1 protein and inhibit the expression of AQP4 protein， thereby reduce the permeability of blood-brain barrier and relieve encephaledema， and play a protective role in brain of model rats with intracerebral hemorrhage.

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