紧密连接蛋白及神经胶质原纤维酸性蛋白在糖尿病大鼠视网膜的表达变化及其与血-视网膜屏障功能的关系  

Changes of tight junction protein and GFAP in the retina of experimental diabetic rats and their relationship with blood aqueous barrier

作　　者：马红婕[1] 罗燕[1] 王敏[2] 梁小玲[1] 黄创新[1] 李涛[1] 丁小燕[1] 唐仕波[1] 

机构地区：[1]中山大学中山眼科中心,广州510060 [2]美国耶鲁大学血管生物及移植中心

出　　处：《中华眼科杂志》2007年第5期397-401,共5页Chinese Journal of Ophthalmology

基　　金：“十五”国家科技攻关计划资助项目（2004BA702B）

摘　　要：目的研究糖尿病鼠视网膜内皮细胞间紧密连接蛋白Occludin及神经胶质原纤维酸性蛋白（GFAP）的表达改变及其与血-视网膜屏障（BRB）的关系。方法链脲佐菌素腹腔注射建立大鼠糖尿病模型1、3、6个月后行伊凡思蓝（EB）注射评价血．视网膜屏障破坏的形态学改变。并行免疫荧光组织化学观察Occludin及GFAP的表达变化。结果1个月时大鼠视网膜中神经纤维层及节细胞层中GFAP表达明显增高，Occludin网线状荧光排列紊乱，但未见荧光强度减弱及中断。3—6个月GFAP阳性的Mtiller细胞逐渐增多，Occludin表达减弱且连续性中断的范围不断扩大。EB注射显示血-视网膜屏障损害呈现同步的发展趋势。结论在糖尿病视网膜病变早期星形胶质细胞的活化可能在维持BRB功能中起重要作用，病情发展Mtiller细胞活化使BRB的完整性进一步破坏。Objective To investigate the changes of vascular endothelial cell tight junction protein （occludin） and glial cell morphology as well as their relationship with blood-retinal barrier （BRB） in the retina of diabetic rats. Methods The distribution of occludin and GFAP were explored by immunofluorescence histochemical studies in the retina of streptozotocin （STZ）-diabetic rats and agematched control rats. Evans blue was used to evaluate the impairment of BRB. Results GFAP immunoreactivity was limited to ganglion cell layer and nerve fiber layer in the control retina. GFAP immunoreactivity was significantly increased in ganglion cell layer and nerve fiber layer in one month diabetic rats. GFAP positive Maller cells were increased in three months and six months diabetic rats. Occludin immunoreactivity progressively decreased in three months and six months diabetic rats but not in the one month diabetic rats. Evans blue injection showed a progressive impairment of BRB. Conclusions Astrocytes activation in the early stage of diabetes plays an important role in the maintaining of the BRB function. But the activation of Mailer cells in the later stage destroyed the BRB eventually. These changes are consistent with the concept that BRB changes caused by altered glial-endothelial cell interactions contributes to the occurrence of diabetic retinopathy.

关 键 词：糖尿病视网膜病变 神经胶质原纤维酸性蛋白 膜蛋白质类 血视网膜屏障 

分 类 号：R686[医药卫生—骨科学]