血脑屏障紧密连接在人脑胶质瘤中的变化  

Changes of tight junctions of blood-brain barrier in human glioma

作　　者：卢建侃[1] 陈祎招[1] 柯以铨[1] 徐如祥[1] 姜晓丹[1] 王育胜[1] 张发兵[1] 孙新林[1] 

机构地区：[1]南方医科大学珠江医院神经外科,南方医科大学广东神经外科研究所,广东省脑功能修复与再生重点实验室,广州510282

出　　处：《中华神经医学杂志》2010年第5期451-455,共5页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金（30500526）;广东省自然科学基金（5300468）

摘　　要：目的 探讨人脑胶质瘤血脑屏障（BBB）内皮细胞间紧密连接的变化及其可能的分子机制. 方法 将南方医科大学珠江医院神经外科自2008年至2009年切除的胶质瘤和正常脑组织标本分为3组：正常脑组织组（n=6）、低级别胶质瘤组（n=11）与高级别胶质瘤组（n=10）,采用透射电镜观察标本BBB紧密连接的超微结构特征,应用免疫荧光双标染色和RT-PCR分别检测标本紧密连接蛋白Claudin-5和Claudin-5 mRNA的表达. 结果 电镜结果 显示正常脑组织微血管相邻内皮细胞间可见连续条带状的紧密连接.细胞间未见裂隙.低级别胶质瘤中多数微血管内皮细胞间可见连续的紧密连接,未见明显窗口形成.高级别胶质瘤中微血管内皮细胞间紧密连接破坏严重,内皮细胞间可见明显裂隙;免疫荧光双标染色结果 显示正常脑组织中微血管内皮细胞上有大量Claudin-5表达.低级别胶质瘤中微血管内皮细胞上Claudin-5表达略为下降,而高级别胶质瘤中微血管内皮细胞上无明显Clandin-5表达;RT-PCR结果 显示高级别胶质瘤Claudin-5 mRNA表达低于正常组脑组织和低级别胶质瘤,差异有统计学意义（P〈0.05）. 结论 在脑胶质瘤发生发展过程中.胶质瘤细胞可以导致BBB内皮细胞间紧密连接蛋白Claudin-5的表达下降及BBB紧密连接结构的破坏,而紧密连接蛋白Claudin-5这一分子元件的表达下降可能是紧密连接结构受到破坏的重要分子机制.Objective To investigate the changes and the molecular mechanism of tight junctions of blood-brain barrier （BBB） in human glioma. Methods A retrospective analysis was conducted in 21 patients with glioma of different grades and 6 healthy adults and thus we divided them into normal tissue group （n=6）, low-grade glioma group （n=11） and high-grade glioma group （n=10）.Each group was sampled for ultrastructural observation of the tight junctions of BBB using transmission electron microscope. Double immunofluorescence staining and RT-PCR were used to observe andanalyze the protein and mRNA expressions of Claudin-5 in the glioma, respectively. Results In normal brain tissues, the para-cellular cleft between the adjacent endothelial cells was sealed by continuous strands of tight junctions. In low-grade glioma, most of the tight junctions were intact and no fenestration was found in the endothelium. In high-grade glioma, the amount of pinocytosis vesicle was increased and significant paracellular cleft was found between the adjacent endothelial cells; in addition,typical fenestrations were found in the endothelial cells. Double immunofluorescence staining showedstrong expression of Claudin-5 in the microvascular endothelial cells in the normal brain tissues but weakexpression of that in the high-grade glioma. In the low-grade glioma, expression of Claudin-5 wasdecreased slightly in the microvascular endothelial cells. Compared with the high-grade glioma, the low-grade glioma and normal brain tissues showed significantly higher mRNA expression level of Claudin-5 （P〈0.05）. Conclusion In the development of brain glioma, glioma cells can decrease the expressions of Claudin-5 and interrupt the continuity of the tight junctions in BBB; and the decrease of Claudin-5 may be one of the important molecular mechanisms explaining the paracellular cleft of tight junction in BBB.

关 键 词：神经胶质瘤 血脑屏障 紧密连接 CLAUDIN-5 

分 类 号：R739.41[医药卫生—肿瘤]