Notch-1及Delta样配体4在糖尿病大鼠早期视网膜中的表达

Expression of Notch-1 and Dll-4 in retina of diabetic rats at early stage

目的探讨糖尿病早期大鼠视网膜中Notch-1与Delta样配体4(Dll-4)的表达变化,及其与血管内皮生长因子受体-2(VEGFR-2)的关系。方法健康雄性成年大鼠60只,分为正常对照(NC)组,糖尿病1个月(DM 1 m)组、2个月(DM 2 m)组及3个月(DM 3 m)组。免疫组织化学法和RT-PCR检测视网膜中Notch-1、Dll-4、VEGFR-2的表达。结果免疫组织化学结果显示,糖尿病大鼠Notch-1、Dll-4、VEGFR-2在视网膜中染色范围较正常大鼠广。RT-PCR结果显示,DM 2 m组、DM 3 m组Dll-4mRNA表达较NC组升高(P<0.05),DM 1 m组、DM 2 m组、DM 3 m组Notch-1 mRNA、VEGFR-2mRNA表达较NC组升高(P<0.05)。Dll-4 mRNA与VEGFR-2及Notch-1呈正相关(r=0.80、0.89,P<0.01),Notch-1与VEGFR-2 mRNA表达呈正相关(r=0.88,P=0.00)。结论糖尿病大鼠早期的视网膜中,Notch-1、Dll-4表达升高,与VEGFR-2表达基本一致,表明糖尿病早期Notch信号通路参与调控视网膜的变化,这种调控作用也许和VEGF通路有关。

Objective To observe the expression of the Noteh=l and Delta like 4（Dll-4） in retina of early stage diabetic rats,and its relationship with vascular endothelial growth factor receptor 2 （VEGFR- 2）. Methods A total of g0healthy adult male rats were enrolled in this study and randomly divided into 4 groups：normal control group, diabetes mellitus with 1 month duration （DM 1 m） group, diabetes mellitus with 2 months duration （DM 2 m） group,and diabetes mellitus with 3 months duration （DM 3 m） group. The expression of Notch-l, Dll-4, VEGFR-2 in retina were detected by immunohistochemical and RT-PCR method. Results The immunohistochemical results showed that Notch-1, Dll-4, and VEGFR-2 expressed more widely in diabetic rats retina than in normal rat. Real time PCR showed that the expression of Dll-4 mRNA were mRNA higher in DM 2 m group and DM 3 m group than in normal group（P〈0. 05）. Notch- 1 and VEGFR-2 mRNA were expressed significantly higher in the DM 1 m group,DM 2 m group and DM 3 m group than in normal rats（P〈0. 05）. The spearman correlation analysis showed that, the expression of mRNA between VEGFR2 and Dll-4, Notchl and Dll-4, Notchl and VEGFR2 were positively correlated （P = 0. 00 ）, and the correlation, coefficient was 0. 80, 0.89, 0. 88 respectively. Conclusion The expression of Notch-1 and Dll-4 are increased in retina of the early stage diabetic rats, and related with VEGFR-2. Notch-1 ,Dll-4 may play a regulatory role in of early diabetic, which may be associated with VEGFR-2 pathway.