腦血疏口服液對腦出血模型大鼠腦組織ZO-1和AQP4表達的影響

王曉峰　田超　張巖　袁夢晨　張涵萊　王麗琴　安娜　高永紅

[摘要] 目的 觀察腦血疏口服液對大鼠腦出血模型腦組織血腦屏障緊密連接蛋白1（ZO-1）、水通道蛋白4（AQP4）表達的影響。 方法 采用尾狀核注射膠原蛋白酶Ⅶ建立腦出血模型。采用隨機數字表法將8周齡SPF級健康雄性SD大鼠分為假手術組、模型組、腦血疏組，每組8只。腦血疏組按照0.27 mL/（100 g·d）進行灌胃給藥，假手術組及模型組分別給予等量生理鹽水。造模后7 d，HE染色法觀察大鼠血腫周圍組織病理形態學改變，透射電鏡法觀察超微結構。Western blot檢測各組血腫周圍腦組織ZO-1、AQP4的表達變化。 結果 與假手術組比較，腦出血7 d模型組HE染色出血灶大片壞死，血腫周圍細胞腫脹變性，核結構不清晰;透射電鏡中可見腦血管與周圍組織間隙增寬，且星形膠質細胞足突水腫明顯;模型組大鼠腦組織中ZO-1蛋白表達量降低，AQP4蛋白表達量增加（P < 0.05）。與模型組比較，腦血疏組病理形態結構明顯改善，ZO-1蛋白表達量明顯升高，AQP4蛋白表達量顯著降低（P < 0.05）。 結論 腦血疏口服液能夠有效促進大鼠腦出血后ZO-1蛋白的表達，抑制AQP4蛋白的表達，降低血腦屏障的通透性，減輕腦水腫，對腦出血后腦組織發揮保護作用。

[關鍵詞] 腦血疏口服液;腦出血;緊密連接蛋白1;水通道蛋白4

[中圖分類號] R743.34? ? ? ? ? [文獻標識碼] A? ? ? ? ? [文章編號] 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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