持续高血糖模型小鼠大脑皮质血管周围星形胶质细胞足突的变化  

Changes of perivascular astrocyte foot process in the cerebral cortex of a mouse model of sustained hyperglycemia

作　　者：黄燕 何婧 向阳[2] 王志强[2] 杜果 王庆松 Huang Yan;He Jing;Xiang Yang;Wang Zhi-qiang;Du Guo;Wang Qing-song(Clinical Medical College of Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Neurology,Chengdu Military General Hospital,Chengdu 610083,Sichuan Province,China)

机构地区：[1]西南医科大学临床医学院,四川省泸州市646000 [2]中国人民解放军成都军区总医院神经内科,四川省成都市610083

出　　处：《中国组织工程研究》2018年第20期3218-3223,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金青年项目(81601112);四川省卫计委科学研究项目(16PJ014)~~

摘　　要：背景:持续高血糖可致脑微血管病变及周围神经变病,显著增加脑卒中及神经功能失调的风险。神经血管结构功能紊乱尤其是血管周围星形胶质细胞足突在其发病机制可能中起着至关重要的作用。目的:观察持续高血糖小鼠大脑皮质血管周围星形胶质细胞足突及胶质血管的变化特点及规律,探讨高血糖致脑微血管病变的相关机制。方法:取成年雄性昆明小鼠20只,随机分为对照组和高血糖组,每组10只。以50 mg/kg链脲佐菌素连续5 d腹腔注射制作高血糖模型。采用免疫荧光双重标记星形胶质细胞足突水通道蛋白4及血管基底膜Ⅳ型胶原蛋白观察胶质血管及血管周围星形胶质细胞足突的变化;采用免疫组化法检测星形胶质细胞足突水通道蛋白4及血管基底膜Ⅳ型胶原蛋白水平变化。结果与结论:(1)与对照组相比,高血糖组星形胶质细胞足突水通道蛋白4与血管基底膜Ⅳ型胶原蛋白共定位比例减少,星形胶质细胞与血管基底膜分离(P<0.05),且水通道蛋白4和Ⅳ型胶原蛋白的表达量均减少(P<0.05);(2)与对照组相比,免疫组化法显示高血糖组血管周围星形胶质细胞足突水通道蛋白4和血管基底膜Ⅳ型胶原蛋白表达量减少(P<0.05);(3)结果提示,持续高血糖可致胶质血管破坏、神经血管单元和血脑屏障改变,其机制可能与血管周围星形胶质细胞足突水通道蛋白4减少有关。BACKGROUND： Sustained hyperglycemia can induce cerebral microvascular disease and peripheral neuropathy, which significantly increases the risk of stroke and neurological dysfunction. Astrocyte foot process around the cerebral microvessels may play a vital role in the pathogenesis of sustained gyperglycemia.OBJECTIVE： To observe the changes of perivascular astrocyte foot process and gliovascular interface in cerebral cortex of mice with sustained hyperglycemia, and to investigate the mechanism of hyperglycemia-induced cerebral microvascular diseases. METHODS： Twenty healthy adult male Kunming mice were randomly divided into two groups： control group and hyperglycemia group. The hyperglycemia was induced by intraperitioneal injection of streptozotocin（50 mg/kg） for 5 consecutive days. The expression levels of aquaporin-4 in the astrocyte foot process and collagen type IV in the vascular basement membrane were detected by double immunofluorescent staining to observe the changes in perivascular astrocyte foot process and gliovascular interface. The expression levels of aquaporin-4 in the astrocyte foot process and collagen type IV in the vascular basement membrane were determined by immunohistochemistry. RESULTS AND CONCLUSION： Compared with the control group, in the hyperglycemia group, there was a significant decrease in the colocalization of aquaporin-4 in the astrocyte foot process and collagen type IV in the vascular basement membrane（P〈0.05）, and the expression levels of aquaporin-4 and collagen type IV were significantly decreased（P〈0.05）. Immunohistochemistry results showed that the expression levels of aquaporin-4 in the astrocyte foot process and collagen type IV in the vascular basement membrane in the hyperglycemia group were significantly lower than those in the control group（P〈0.05）. These results indicate that sustained hyperglycemia can destroy gliovascular interface, and result in neurovascular unit and blood brain barrier dysfunction, probably by reducing the express

关 键 词：高血糖症 基底膜 模型 动物 组织工程 高血糖 星形胶质细胞足突 水通道蛋白4 血管基底膜 胶质血管连接 神经血管单元 链脲佐菌素 随机血糖 Ⅳ型胶原蛋白 2型糖尿病 血脑屏障 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]