白细胞介素17在糖尿病大血管中的表达及白藜芦醇的干预机制  

Expression of interleukin-17 in diabetic macroangiopathy and the mechanism of intervention with resveratrol

作　　者：楼旭丹[1] 汪海东[1] 夏世金[2] 顾芹[1] 

机构地区：[1]复旦大学附属华东医院内分泌科,上海200040 [2]复旦大学附属华东医院、上海市老年医学研究所

出　　处：《中华内分泌代谢杂志》2013年第8期700-704,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：上海市科委科技发展基金基础研究重点课题（10JC1404800）,国家自然科学基金面上项目（31171129）

摘　　要：目的研究糖尿病大鼠主动脉白细胞介素17（IL-17）的表达及白藜芦醇的干预效应，并从表观遗传学角度探讨IL-17参与糖尿病血管病变的潜在机制和白藜芦醇的保护性机制。方法将100只SD大鼠分为对照组（NC）、正常干预组（NB）、糖尿病组（DM）和糖尿病干预组（DB），NB和DB组用白藜芦醇进行干预．通过免疫组化对IL-17表达进行组织学定位并测量大鼠腹主动脉壁厚度，采用Western印迹、实时PCR及甲基化特异性PCR技术，分别比较各组大鼠主动脉IL-17蛋白、mRNA及基因启动子区DNA甲基化水平的差异。结果免疫组化染色显示IL-17主要表达于DM组大鼠主动脉内膜，DM组与NC和DB组相比腹主动脉壁明显增厚（P〈O．05）；DM组IL-17蛋白及mRNA表达水平较NC组增高（P〈0．05），而NB和DB组则分别较NC和DM组下调：同时DM组IL-17DNA甲基化水平显著低于NC组（P〈O．01），而NB和DB组甲基化水平分别较NC和DM组上调。结论糖尿病大鼠主动脉IL-17表达增强，提示IL-17参与糖尿病大血管病变的炎症反应过程，白藜芦醇可抑制IL-17的表达，可能对糖尿病大血管病变有保护作用，两者的发生机制可能通过调控IL-17基因启动子区DNA甲基化水平来实现。Objective To study the expression of interleukin-17 （ IL-17 ） in diabetic rat aorta a,ad the effect of intervention with resveratrol, meanwhile, to explore the potential mechanisms of IL-17 induced diabetic vascular diseases and the protective role played by resveratrol in the epigenetic field. Methods The experiment was carried out in 4 groups ： normal control group（ NC ） , normal interventional group （ NB ）, diabetic group （ DM ） , and diabetic interventional group（DB） , NB and DB groups were intervened with resveratrol. Immunohistochemistry was used to observe the histological localization of IL-17 and to measure the thickness of rat abdominal aorta. Western blotting, real-time PCR, and methylation-specific PCR were used respectively to compare the expression of IL-17 protein and mRNA, as well as DNA methylation in 4 groups. Results IL-17 mainly expressed in arterial intima of diabetic rats, the abdominal aorta in DM group was obviously thicker than that in NC and DB groups（ P〈0.05 ）. IL-17 protein and mRNA expressions in DM group were significantly higher than NC group（ P〈0.05 ） , and were reduced in NB and DB groups compared with NC and DM groups respectively. While DNA methylation levels of IL-17 in DM group were significantly lower than NC group（ P〈0.01 ）, however, the levels in NB and DB groups were elevated accordingly as compared with corresponding groups. Conclusions The increased levels of IL-17 in aorta of diabetic rats suggests that IL-17 is involved in the process of inflammatory responses to diabetic macrovascular diseases, while resveratrol could inhibit the expression, it may play a role in protecting aorta, and the regulation of IL-17 gene promoter DNA methvlation levels may be the potential mechanism underlving these two ohenomena.

关 键 词：白细胞介素17 糖尿病大血管病变 白藜芦醇 DNA甲基化 

分 类 号：R587.2[医药卫生—内分泌]