自噬与PI3K/Akt/mTOR通路Cross-talk在胰岛素抵抗中的作用及黄连温胆汤的干预机制

胰岛素抵抗（IR）是代谢综合征的重要发病机制，改善IR是防治代谢综合征必须攻克的难题，近年来研究表明IR和自噬活性具有相关性，胰岛素受体后信号通路PI3K/Akt/mTOR与自噬信号调控途径存在Cross-talk，其中Akt磷酸化水平起关键作用。古方黄连温胆汤治疗代谢综合征疗效显著，基于前期实验结果，黄连温胆汤具有调控胰岛素受体后信号通路的作用，本项目拟构建胰岛素抵抗模型，进一步在自噬与PI3K/Akt/mTOR通路Cross-talk的基础上寻找黄连温胆汤改善IR的作用靶点，验证如下假说：黄连温胆汤可能通过调控Akt磷酸化水平干预PI3K/Akt/mTOR通路与自噬信号途径间的Cross-talk，从而调节该通路并维持自噬稳态，改善IR。本项目从分子水平更深入地阐明古代经典名方黄连温胆汤改善IR的作用机制，丰富该方的现代研究内容，为该方的开发及临床推广提供详实的实验依据。

Insulin resistance (IR) is the main pathophysiology basis of metabolic syndrome, improving IR is a difficult problem to overcome. Recent studies have shown that IR and autophagy activity are correlated, PI3K/Akt/mTOR signaling pathway and autophagy exist cross-talk, its key point is Akt phosphorylation levels. The curative effect of Huanglianwendan Decoction on metabolic syndrome is remarkable. Based on the the early research results that Huanglianwendan Decoction’s efficacy material base and its regulation of insulin receptor signaling pathways, this project intends to build the insulin resistance model, and to find the target of improving IR on the basis of cross-talk between autophagy and PI3K/Akt/mTOR pathway. To verify the following scientific hypothesis: Huanglianwendan Decoction may control PI3K/Akt/mTOR signaling pathway and maintain autophagy steady state at the same time by regulating Akt phosphorylation level, thus improving the IR. This project further clarify the molecular level of Huanglianwendan Decoction to improve the mechanism of IR, enriching the content of the party of modern research, to provide a detailed experimental basis for the development and clinical promotion of Huanglianwendan Decoction.