细胞外基质纤维连接蛋白和层粘连蛋白在糖尿病大鼠视网膜微血管病变表达的研究

Study of fibronectin and laminin expression in the ret inal microvessels of diabetes-like retinopathy in rats

目的 探讨细胞外基质纤维连接蛋白 (FN )、层粘连蛋白 (LN )与糖尿病视网膜病变(DR)的关系。 方法 雄性Wistar大鼠 3 0只 ,随机分为糖尿病模型组 (DR组 ,n =2 0 )及正常对照组 (对照组 ,n =10 )。DR组大鼠腹腔注射链脲佐菌素 (STZ) 60mg/kg ,制备DR微血管病变模型。180d时处死大鼠 ,取外周血作血液流变学检查 ,眼球用 3 %胰酶消化 ,制成视网膜血管铺片 ,进行FN、LN免疫组织化学染色 ,并采用LEICA—Q550IW计算机图像分析系统定量分析FN、LN在视网膜微血管中的表达及分布。观察DR的形态学改变 ,计数内皮细胞与周细胞的比例。 结果 图像分析显示 :DR组FN、LN含量表达与对照组比较差异有显著意义 (P <0 0 0 1)。形态学观察 :DR组视网膜微血管周细胞减少、内皮细胞增生与对照组比较差异有显著意义 (P <0 0 0 1) ,毛细血管瘤、无细胞毛细血管形成 ,并有较多的白细胞栓塞血管腔。血液流变学检查 :血黏度、红细胞变形能力等改变与正常对照组比较差异均有显著意义 (P <0 0 5或 0 0 1)。 结论 细胞外基质中FN、LN的过度表达 ,介导细胞与细胞及细胞与间质之间相互作用 ,促进视网膜微血管内皮细胞增生、毛细血管瘤形成 ,并导致毛细血管闭锁、基底膜增厚等病理改变 。

ObjectiveTo elucidate the relatiohship between t he expression level of fibronectin (FN) and laminin (LN) in the retinal microves sel wall and the pathogenesis of diabetic retinopathy.MethodsThirty male Wistar rates were randomly divided into the diabetic retionpathy g roup (n=20, DR) and normal control group (n=10, NC). From the streptozot oxin-induced diabetic retinopathy rats the peripheral blood was withdrawn for b lood rheological indexes and the eyeballs were removed for making the retinal va scular network whole mounts and immunostaining for FN and LN with LSAB technique .The expression levels of FN and LN were quantitatively measured by LEICA-Q550 IW computer image ancitysis system. The morphological observation and a differen tial count of the endothelial cells and pericytes were also performed respective ly.ResultsIn the DR group the expression levels of FN and LN were significantly higher. The number of the pericytes and proliferative endoth elial cells decreased and increased significantly respectively compared with the NC group (P<0 01). The capillary aneurysm and acellular capillary as well as the leucocytes-filled thrombosis in the lumens of capillary were also obse rved in DR group. The erythrocyte viscosity and plasma triglyceride had signif icant increase in comparison with NC group (P<0 05 or 0 01). Con clusionThe present results indicate that there might exist a close rel ationship between the diabetic retinopathy and the high expression of FN and LN in the extracellular matrix. The FN and LN overexpress might be an important cau se for DR pathogenesis.