泽泻汤临床降脂效果良好；SREBPs是调节脂质合成限速酶基因的关键转录因子。基于SREBPs报告基因系统，申请人发现泽泻汤中MEA（泽泻单体成分）和BZ-92（白术单体成分）活性贡献度指数最高，协同抑制SREBPs并发挥体外降脂效应，但协同作用机制不明；申请人的前期研究提示MEA和BZ-92可能分别抑制pre-SREPB剪切成熟、促进n-SREBPs降解，初步筛选通路并结合已完成的转录组学研究，提出“MEA调控ER/Caspase-2/S1P抑制pre-SREPB剪切成熟，BZ-92调控miR-27b/Fbxw7促进n-SREBPs的降解发挥协同作用”的假说；拟采用WD小鼠验证MEA和BZ-92体内降脂药效；并利用现代分子生物学技术在体内外正反验证假说，阐释MEA和BZ-92协同调控SREBPs的降脂作用机制。为泽泻汤降脂应用提供科学依据，通过活性成分及组分配伍为复方研究提供思路。

Zexie Decoction has a remarkable lipid-lowering effect in clinical application. Sterol Regulatory Element Binding Proteins (SREBPs) are key transcription factor that regulates lipid-synthesis speed-limiting enzyme genes. Based on the SREBPs reporter system, we found that MEA (ingredient of Zexie) and BZ-92 (ingredient of Baizhu) had the highest activity contribution index contribution in Zexie Decoction, which synergistically inhibited SREBPs and exerted a lipid-lowering effect in vitro. Our previous research suggests that MEA and BZ-92 may inhibit pre-SREPB maturity and promote the degradation of n-SREBPs, respectively. Combined with completed transcriptomics studies, we hypothesis that MEA regulates ER/Caspase-2/S1P to inhibit pre-SREPB maturation, and BZ-92 regulates miR-27b/Fbxw7 promote n-SREBPs degradation and play a synergistic lipid-lowering effect. This project intends to explore the synergistic effects of MEA and BZ-92 on lipid, insulin resistance and fatty liver in western type diet (WD) induced hyperlipidemia mice and further investigate the efficacy of synergistic effect in vivo. And using modern molecular biology techniques to investigate the hypothesis in vitro and in vivo, elucidate the possible mechanism of MEA and BZ-92 synergistic lipid-lowering regulate of SREBPs. The above research will provide scientific basis for clinical application of Zexie Decoction to reduce lipids, and provides ideas of Chinese herbal compound research for compound research through active ingredients and group assignment.