肾素原受体在糖尿病视网膜病变中的作用及其机制研究  

The role of the RAS system in diabetic retinopathy

作　　者：王玮[1] 梁坤[1] 蒋正轩[1] 彭畅[1] 陶黎明[1] 

机构地区：[1]安徽医科大学第二附属医院眼科,合肥230601

出　　处：《安徽医科大学学报》2015年第6期761-765,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81300755);安徽高校省级自然科学基金重点项目(编号:KJ2013A147)

摘　　要：目的观察糖尿病视网膜病变发生过程中肾素原受体(PRR)及血管紧张素Ⅱ受体2(AT2R)的表达水平及视网膜神经细胞凋亡情况,阐明PRR与糖尿病视网膜神经细胞凋亡的关系。方法建立链尿佐菌素诱导的糖尿病SD大鼠模型,建模成功后分别在4周、8周和12周用免疫组化法检测CD14及8-羟脱氧鸟苷分子的表达,检测糖尿病及对照组视网膜AT2R、PRR mRNA的表达及细胞外信号调节激酶(ERK1/2)、磷酸化ERK1/2(p-ERK1/2)蛋白的表达。结果各病程SD大鼠视网膜AT2R和PRR的mRNA表达水平较对照组明显升高(P<0.05),随病程的延长表达量随之增多。病程越长糖尿病组大鼠视网膜组织凋亡细胞数量越多,各阶段病程CD14染色未见明显新生血管。通过相关性分析显示,PRR和AT2R表达水平与神经节细胞凋亡相关。各病程大鼠视网膜ERK1/2、p-ERK1/2蛋白的表达量显著高于对照组。结论糖尿病视网膜病变中PRR和AT2R的表达与大鼠糖尿病视网膜病变的神经节细胞凋亡相关,可能通过增加ERK的磷酸化水平发挥功能作用。Objective Observing the pattern recognition receptor（PRR）and angiotensin Ⅱreceptors2（AT2R）＆nbsp;expression level in rennin-angiotensin system,and retinal nerve cells apoptosis in the process of diabetic retinopa-thy,in order to explore the relationship between the PRR receptor and retinal nerve cells apoptosis in diabetic rats. Methods First,we built the diabetic rat model by using streptozocin. Second,the expressions of CD14 and 8-OHdG were detected by immunohistochemical. Third,the mRNA expressions of AT2R and PRR after 4,8 and 12 weeks of diabetes and normal control group were detected,respectively. Last,the levels of extracellular signal-reg-ulated kinase（ERK）1 / 2,p-ERK1 / 2 proteins were measured by Western blot. Results AT2R and PRR mRNA expression levels in diabetes groups were higher than the control group significantly,and the expression level was increasing with the extension of the course（P 〈 0. 05）. The longer the course of the disease,the more rats retinal cells apoptosis in diabetes group. There were less new blood vessels in diabetes group as the CD14 dyeing was neg-tive. Through correlation analysis,PRR and AT2R expression levels were associated with the ganglion cell apopto-sis. In diabetes groups ERK1 / 2,p-ERK1 / 2 protein expressions were significantly higher than the control group. Conclusion AT2R and PRR mRNA expression levels are related with the cell apoptosis of rats with diabetic reti-nopathy. RAS may play a key role in diabetic retinopathy through increasing the phosphorylation of ERK level.

关 键 词：糖尿病视网膜病变 肾素血管紧张素系统 ERK信号通路 

分 类 号：R587.26[医药卫生—内分泌]