粘附分子与实验性糖尿病视网膜病变的初步研究

A preliminary study on the relationship between adhesion molecules and diabetic retinopathy in diabetic rats

目的 探讨粘附分子在糖尿病视网膜病变（ Ｄ Ｒ） 发病中的作用。方法 应用链脲佐菌素（ Ｓ Ｔ Ｚ） 建立糖尿病大鼠模型，分别于成模后３ 个月和６ 个月时经光镜和透射电镜观察视网膜的形态学改变。应用免疫组化方法及微机图像处理系统，对视网膜组织细胞间粘附分子１（ Ｉ Ｃ Ａ Ｍ１） 及整合素族 Ｃ Ｄ６１ 的分布与含量进行动态观察与分析；应用流式细胞术测定循环血中粒细胞表面β２ 整合素族 Ｃ Ｄ１１ａ 、 Ｃ Ｄ１１ｂ 的表达。结果 病变３ 月组已有 Ｉ Ｃ Ａ Ｍ１ 及 Ｃ Ｄ６１ 的表达明显增加，并随病程延长表达进一步增多，而在正常对照组未见明显表达（ Ｐ＜ ０ ．０１） 。糖尿病大鼠粒细胞表面抗原 Ｃ Ｄ１１ａ 、 Ｃ Ｄ１１ｂ 阳性细胞群体所占的比例较对照组显著升高（ Ｐ＜ ０ ．００１） 。视网膜毛细血管基底膜厚度与 Ｉ Ｃ Ａ Ｍ１ 、 Ｃ Ｄ６１ 表达灰度值呈显著正相关（ ｒ ＝ ０ ．７７２ ，０ ．６９４ ， Ｐ＜ ０ ．０５） 。结论 粘附分子与其配基过度表达，加重内皮细胞损伤及微血管栓塞，很可能是导致 Ｄ Ｒ 发生中进展性微血管病变的重要因素之一。

Objective To explore the role of adhesion molecules in the development of diabetic retinopathy (DR) in diabetic rats. Methods Diabetes model was established in Wistar rats by induction with streptozotocin (STZ). The early changes of retinae were examined using light microscope and transmission electron microscope. Immunohistochemistry was employed to analyse the expression of ICAM 1 and CD61 (integrin β 3 chain) in diabetic retinae. Flow cytometric analysis was applied to detect the expression of CD11a (LFA 1 α chain) and CD11b (MAC 1 α chain) on the surface of neutrophils isolated from the systemic circulation. Results The early stages of ocular lesions occured in the retinae of diabetic rats at 3 months. The nondiabetic retinae demonstrated relatively little ICAM 1 immunoreactivity and CD61 immunoreactivity was rarely observed. While ICAM 1 and CD61 immunoreactivity was consistently greater than that observed in normal retinae (P<0.01). The increased expression occurred before visible retinal pathological changes. A significant increase in number of neutrophils isolated from systemic circulation, which expressed CD11a/CD11b was found in the pathologic group as compared with the control group (P<0.001). The thickness of capillary basement membrane was correlated positively with the immunoreactivities of ICAM 1 and CD61 in the retinae. Conclusion The results indicate that increased intercellular adhesion molecules may be the main inductive mediator and play an important role in the progression of diabetic retinal microangiopathy.