葛根芩连汤逆转T2D大鼠脂肪组织脂代谢基因高甲基化的作用

项目名称： 葛根芩连汤逆转T2D大鼠脂肪组织脂代谢基因高甲基化的作用

项目编号： No.81503315

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 彭淑红

作者单位： 江西中医药大学

项目金额： 18万元

中文摘要： 2型糖尿病(Type 2 Diabetes，T2D)是一种全球性的代谢失调病，严重危害人类健康。临床上中药复方葛根芩连汤治疗T2D疗效确切，但机制尚不明确。现代研究表明：①T2D病人及高脂饮食小鼠脂肪组织脂代谢基因呈现高甲基化；②葛根芩连汤主要成分能逆转DNA甲基化；基于以上二点，本项目提出“逆转T2D大鼠脂肪组织脂代谢基因的高甲基化是葛根芩连汤治疗T2D的机制之一”。据此，本课题拟通过复制T2D大鼠模型，采用甲基化DNA免疫共沉淀测序 (MeDIP-Seq)和荧光定量PCR技术确定脂肪组织中受DNA甲基化调控的候选脂代谢基因；然后采用重亚硫酸盐测序的方法结合候选基因的表达数据，明确葛根芩连汤作用的具体靶基因，从而论证该复方基于DNA甲基化发挥疗效的机制。本研究将为葛根芩连汤治疗T2D提供理论依据，同时为中药复方治疗代谢综合征的复杂机制研究提供表观遗传学的新视角。

中文关键词： 2型糖尿病；葛根芩连汤；DNA甲基化；脂代谢

英文摘要： Type 2 diabetes (T2D) is a metabolic disorder with a rapidly increasing worldwide prevalence which is very harmful for human health. Gegen Qinlian Decoction (GQD) as a Chinese herb compound was effective in the treatment of T2D. However its mechanism has barely been elucidated. Some studies showed that 1) some chemical ingredients of GQD reversed methylation state of gene promoters in some diseases, 2) and in T2D and high-fat-fed mice, the genome-wide significant adipocyte hypermethylated DMRs were near genes that were significantly overrepresented in lipid metabolic pathway. Therefore, we put forward a hypothesis that reversing hypermethylated lipid metabolic genes in fatty tissue is one mechanism of GQD to treat T2D. To support the hypothesis, firstly, candidate lipid metabolic genes will be identified by methylated DNA immunoprecipitation sequencing (MedIP-seq) and real-time PCR after successfully replicated T2D rat models. Then target genes regulated by GQD will be demonstrated via bisulfite sequencing PCR combined with candidate genes expression data. Consequently, the mechanism for GQD to treat T2D involving the DNA methylation will be suggested. The research could provide a theoretical basis for clinical application of GQD, and it may propose a new perspective from epigenetics to study complicated mechanisms of the Chinese herb compound to treat metabolic syndrome as well.

英文关键词： Type 2 Diabetes;Gegen Qinlian Decoction;DNA methylation;Lipid metabolism