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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。
RAGE-RAGE (RAGE) signal axis activated by AGEs and 4-hydroxynealdehyde (4-HNE) and other active carbonyl compounds (RAGEs) Degenerative diseases, cancer and other degenerative diseases play a crucial role in the development. In this study, diabetic mice model was established by intraperitoneal injection of alloxan to explore the expression of RCCs-RAGE axis in Epigallocatechin Gallate (EGCG) -hibited alloxan-induced diabetic mice. Diabetic mice were randomly divided into model group, low-dose EGCG group (10 mg · kg-1 · d-1) and medium dose EGCG group (20 mg · kg-1 · d-1) And EGCG high-dose group (30 mg · kg-1 · d-1). Mice were treated with EGCG for 12 days. The serum glucose, insulin and soluble RAGE (sRAGE), carbonyl protein and AGEs were measured. The relative expression of RAGE in kidney was detected by QPCR. RAGE protein and 4-HNE content. The results showed that, compared with diabetic model group, EGCG can effectively inhibit the inflammatory response cascade mediated by AGEs-RAGE signal axis by inhibiting the generation of toxic active carbonyl compounds such as 4-HNE, AGEs and other RCCs, increasing the serum concentration of sRAGE, Of oxidative stress, showing good protection of diabetic mice activity. This study revealed a new perspective of EGCG inhibition of RCCs-RAGE signal axis is one of the potential mechanisms of its prevention and treatment of decay-related diseases.