EGCG抑制四氧嘧啶致糖尿病小鼠RCCs-RAGE信号轴表达的研究  

Study on the Inhibition Effects of EGCG on the Expression of RCCs-RAGE Axis in Diabetic Mouse Induced by Alloxan Monohydrate

作　　者：钟源[1] 张静[1] 刘仲华[1,2,3] 蔡淑娴[1,3] 罗国安[4] 黄建安[1,2] 吴香兰[1] 瞿绍明 金丽莎[1] 

机构地区：[1]湖南农业大学茶学教育部重点实验室,湖南长沙410128 [2]国家植物功能成分利用工程技术研究中心,湖南长沙410128 [3]北京大学医学部基础医学院,北京100191 [4]清华大学化学系生命有机磷与化学生物学教育部重点实验室,北京100084

出　　处：《茶叶科学》2014年第2期156-164,共9页Journal of Tea Science

基　　金：国家自然科学基金(31100501);中国博士后基金(2012M520128);教育部创新团队计划项目(201042);国家茶叶产业技术体系项目(CARS-23-C);国家科技支撑计划(2011BAD01B01)

摘　　要：糖基化终末端产物(AGEs)和4-羟基任烯醛(4-HNE)等活性羰基化合物(Reactive carbonyl compounds,RCCs)激活的RCCs-RAGE(Receptor for AGEs,RAGE)信号轴在糖尿病、神经退行性疾病、癌症等衰退性疾病的发生发展中起了关键性的作用。本研究采用四氧嘧啶腹腔注射的方法建立糖尿病小鼠模型,探讨表没食子儿茶素没食子酸酯(Epigallocatechin Gallate,EGCG)阻抑四氧嘧啶致糖尿病小鼠RCCs-RAGE轴表达的活性。糖尿病小鼠按其体质量与血糖值随机均匀分为模型组、EGCG低剂量组(10 mg·kg-1·d-1)、EGCG中剂量组(20 mg·kg-1·d-1)和EGCG高剂量组(30 mg·kg-1·d-1)。小鼠连续灌胃EGCG 12 d后,检测小鼠血清中血糖值、胰岛素和水溶性RAGE(sRAGE)浓度、羰基蛋白含量、AGEs荧光值,QPCR检测肾脏RAGE基因相对表达量,Western blot方法检测肾脏RAGE蛋白和4-HNE含量。结果显示,与糖尿病造模组相比,EGCG通过抑制4-HNE、AGEs等RCCs毒性活性羰基化合物的生成,增加sRAGE血清浓度,抑制AGEs-RAGE信号轴介导的炎症瀑布反应,有效缓解了机体的氧化应激压力,表现出很好的保护糖尿病小鼠的活性。本研究从一个新角度揭示了EGCG抑制RCCs-RAGE信号轴是其防治衰退性相关疾病的潜在作用机制之一。The RCCs-RAGE signal axis induced by RCCs, including AGEs and 4-HNE, plays a key role in degenerative diseases, such as diabetes and cancer. To study on inhibiting activity effects of EGCG on RCCs-RAGE, diabetic mouse induced by intraperitoneal injection Alloxan monohydrate were divided into model group, EGCG-L （10 mg·kg^-1·d^-1） group, EGCG-M （20 mg·kg^-1·d^-1） group, and EGCG-H （30 mg·kg^-1·d^-1） group according to body weight and blood glucose. After 12 days’ administration respectively to three groups of diabetic mouse by gavage, blood glucose value, insulin, sRAGE concentration, carbonyl content and fluorescence value of AGEs in serum were determinde, while the expressions of RAGE gene in kidney were detected by QPCR, RAGE protein and 4-HNE experiment by western bolt. Result showed, compared to model group, EGCG could improve diabetes symptom of mouse by significantly decreasing the formation of RCCs, including carbonyl, 4-HNE and AGEs, increasing the concentration of sRAGE in serum, inhibiting the inflammation reaction induced by RCCs-RAGE, and alleviating the oxidation stress effectively. The study revealed that EGCG inhibited the RCCs-RAGE signal axis may be one of the potential mechanisms in the treatment of degenerative diseases.

关 键 词：糖尿病 活性羰基化合物 晚期糖基化终末端产物受体 

分 类 号：R587.1[医药卫生—内分泌]