急性脑出血血肿周围组织水通道蛋白-4表达与血脑屏障损伤的关系  

Relationship between aquaporin-4 expression and blood-brain barrier damage after acute experimental intracerebral hemorrhage

作　　者：唐宇平[1] 蔡定芳[1] 刘军[1] 李文伟[1] 陈依萍[1] 闻名[1] 

机构地区：[1]复旦大学中山医院中西医结合研究所神经病学研究室,上海200032

出　　处：《中华神经科杂志》2005年第11期704-708,共5页Chinese Journal of Neurology

基　　金：上海百人项目资助项目(BR97016);国家自然科学基金资助项目(30271639)

摘　　要：目的研究急性脑出血血肿周围组织水通道蛋白-4表达与血脑屏障损伤之间的关系。方法采用立体定向注射无肝素自体动脉血制作大鼠脑出血模型,对脑含水量、血脑屏障损害进行观察,RT-PCR和免疫印迹检测水通道蛋白-4 mRNA和蛋白表达,同时观察参与紧密连接的咬合蛋白(occ lud in)和带状闭合蛋白-1(zona occ ludens-1,ZO-1)表达和水通道蛋白-4表达的相关关系。电镜下观察不同时间点血脑屏障和神经星形胶质细胞终足改变。结果电镜提示出血后6 h血脑屏障紧密连接未破坏,但神经胶质细胞终足已经肿胀。与假手术组相比,此时的脑出血血肿周围组织大鼠水通道蛋白-4表达增高(P<0.05):脑出血3 h水通道蛋白-4 mRNA开始增强(吸光度比值1.05±0.13),水通道蛋白-4蛋白6 h开始增强(0.62±0.05),第3天达峰值(1.46±0.02)。电镜和伊文蓝显示血脑屏障从12 h才开始明显损害[12 h脑组织伊文蓝含量为(12.91±0.64)μg/g],同时ZO-1和occ lud in蛋白表达减弱,分别为0.71±0.05和0.72±0.04。与水通道蛋白-4蛋白表达呈负相关。结论脑出血后水通道蛋白-4增高和血脑屏障损伤之间存在相关关系;水通道蛋白-4增高和星形胶质细胞肿胀可能是血脑屏障损伤的因素之一。Objective To investigate the relationship between Aquaporin-4（AQP-4） expression and blood-brain barrier damage experimentally after acute intracerebral hemorrhage. Methods The intracerebral hemorrhage （ICH） was established by infusing autoblood into rat caudate nucleus. Brain water content and Evan blue were used to confirm edema, BBB damage. RT-PCR and Western blot were respectively used to evaluate AQP-4 mRNA and protein expression and to observe the correlation between AQP-4 and tight junction protein ZO-1, occludin. Electron microscope was used to explore the level of BBB tight junction damage and astrocyte foot process swelling. Results Electron microscope showed astrocyte foot process swollen without BBB tight junction damage at the 6th hour after hemorrhage. As compared with the sham group, there appeared a significant increase in AQP-4 mRNA and protein expression following ICH （ P〈0.05 ） ： expression of AQP-4 mRNA appeared increased at the 3rd hour （ 1.05±0.13 ） and protein appeared increased （0.62±0.05 ） at the 6th hour following the hemorrhage. Expression of AQP-4 mRNA and protein reached its maximum at the 72th hour （ 1.46±0.02）. Evan blue and electron microscope revealed BBB tight junction began to damage at the 12th hour following the hemorrhage. At the same time, expression of ZO-1 ,occludin（0.71±0.05 and 0.72±0.04, respectively）was decreased and shown a negative correlation with expression of AQP-4. Conclusions BBB damage might have negative correlation with expression of AQP-4 following hemorrhage. Increased espression of AQP-4 and astrocyte foot process swollen might be one of the early cause of BBB damage.

关 键 词：脑出血 水孔蛋白类 血脑屏障 脑水肿 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R743.02[医药卫生—临床医学]