非酒精性脂肪性肝炎（NASH）引起的肝脏和代谢危害日趋严重，但治疗手段有限。中医药治疗NASH效果显著，但作用机制尚不明确。课题组研制的新药降脂颗粒经II期临床试验证实对脂肪肝治疗安全有效，机制探索发现降脂颗粒抑制肝脏代谢性炎症与胆汁酸G蛋白偶联受体TGR5表达升高有关。因此在前期研究基础之上，我们提出“降脂颗粒活化TGR5治疗NASH”的学术假说。为验证这一假说，本项目拟采用体内外实验、高通量分析、细胞转染、基因敲除等手段，探索TGR5-cAMP信号通路相关分子在NASH相关组织的变化规律，阐明降脂颗粒活化TGR5调节胆汁酸平衡、脂质代谢、炎症反应等多途径治疗NASH的作用机理，预期研究结果对促进中医药防治NASH相关疾病的应用有重要价值。

Non-alcoholic steatohepatitis (NASH) causes severe hepatic and metabolic risks in patients, but pharmacological strategies are limited. Traditional Chinese medicine is of significant effect in treating NASH, however, the mechanisms are remain unclear. The herbal compounds Jiangzhi granula developed by our group has been confirmed to be safe and effective in treating of fatty liver disease in a Phase II clinical trial. Mechanisms exploration in our previous studies revealed that bile acid G protein-coupled receptor TGR5 is up-regulated with the improvement of metabolic-related inflammation in Jiangzhi Granula treated animals. Therefore, based on the previous studies, we hypothesized that "Jiangzhi granula may treat NASH via activating TGR5". To verify the hypothesis, we intend to investigate the changes of TGR5-cAMP signaling pathway through both in vivo and in vivo experiments, high-throughput analysis, cell transfection and gene knockout technology, and demonstrate the potential mechanisms under the efficacy of Jiangzhi granula in regulating bile acid pool, lipid metabolism, metabolic inflammation, etc. our work are expecting to be valuable in promoting NASH prevention and treatment with Traditional Chinese Medicine.