早期糖尿病大鼠视网膜血管形态学的改变与血管内皮生长因子的表达

目的观察早期糖尿病大鼠视网膜病变与血管内皮生长因子(VEGF)表达之间的关系,为糖尿病视网膜病变(DR)的临床研究及治疗寻找有效的手段。方法将36只雄性SD雄性大鼠随机分为正常对照组(M)、糖尿病1月组(M1)、2月组(M2)和3月组(M3)。取视网膜标本制成视网膜血管铺片,采用荧光免疫组织化学法观察VEGF的表达,透射电镜观察各组视网膜血管损伤的形态学改变。结果VEGF荧光免疫组化:M1组未见明显表达,M2组9只鼠中有5只表达增强,M3组有8只表达增强。视网膜血管透射电镜观察:M组未见异常改变,从M1组开始出现异常改变,且随着病程延长,改变增加明显,以M3组最为显著,表现为神经节细胞层血管内皮细胞肿胀,向管腔突出,细胞核内异染色质凝集居边,细胞质内线粒体明显肿胀,粗面内质网呈池样扩张,血管周围胶原纤维明显增生,并可见到闭锁的毛细血管。结论糖尿病发展的早期,视网膜超微结构的改变早于VEGF的表达;随着病程进展,VEGF在视网膜上的表达呈逐渐增强的趋势,提示VEGF在早期DR的发生发展中起重要作用。

Expression of vascular endothelial growth factor and injury of retinal cells in early diabetic retinopathy by electromicroscope

Objective To study the effects of vascular endothelial growth factor(VEGF) in early stage diabetic retinopathy and their mechanisms,so as to guide the clinical work theoretically.Methods Thirty-six SD rats were randomly divided into four groups.Nine rats were used as normal controls(M Group).Streptozocin were injected intraperitoneally to induce diabetes for 1 month(M1 Group),2 months(M2 Group),and 3 months(M3 group).At the experimental ends of each group,the rats were over anesthetized and their eyeballs were extracted to make digest preparation.Immunofluorescence were used to investigate the expression of VEGF on retinal blood vessels.Transmission electromicroscopy was used to observe the histology of the retinal vessels.Results VEGF immunofluorescence showed an expression rate of 56% in M2 group and 89% in M3 group.Transmission electromicroscopy showed no change in M Group.However,it showed swelling of endothelial cells,finger like process into the capillary cavity,uneven distribution of heterochromatin in pericytes in M1 Group.Obvious fragmental thickening and splitting of basement membrane,swelling and deformation,finger like process to the capillary cavity,and concentration and margination of heterochromatin in endothelial cells,and swelling and deformation of rough surfaced endoplasmic reticulum and mitochondrion in pericytes were observed in M2 and M3 groups,especially in the latter.Conclusion The expression of VEGF proteins in the retinas of diabetic rats increases with the progression of diabetes.It proves that VEGF plays an important role in the occurrence and development of early diabetic retinopathy.