植物蛋白替代鱼粉引发营养型肝病是导致肉食性鱼类无法高效利用植物蛋白的主要原因之一。前期研究发现，糖脂代谢、胆汁酸代谢紊乱是植物蛋白替代引发施氏鲟营养型肝病的主要原因。胆汁酸是临床上治疗肝胆疾病的靶向药，能够有效治疗糖脂代谢、胆汁酸代谢紊乱引起的肝脂肪变性及纤维化。因此，外源胆汁酸干预可能是缓解植物蛋白替代引发施氏鲟营养型肝病的有效途径。胆汁酸信号对代谢的调控作用依赖于受体。前期研究证明，胆汁酸受体TGR5参与植物蛋白替代引发施氏鲟营养型肝病的调控。但是在鱼类中，该受体对胆汁酸的响应以及在肝病中的调控作用尚不清楚。因此，本项目拟以施氏鲟为研究对象，结合生物化学、分子生物学、细胞生物学、药理学等技术手段，探究TGR5在植物蛋白替代引发营养型肝病不同发展阶段及胆汁酸靶向干预中的功能及调控机制，为肉食性鱼类高效利用植物蛋白以及其他鱼类营养型肝病的治疗提供新思路。

Nutritional liver disease (NLD) caused by plant protein is one of the main factors for limiting plant protein utilization in carnivorous fish. In our previous studies, it was found that glucose and lipid metabolism disorder and bile acid metabolism disorder were the main causes of NLD in Amur sturgeon (Acipenser schrenckii). Bile acid, a targeted drug for the clinical treatment of hepatobiliary diseases, was proved to effectively treat hepatic steatosis and fibrosis caused by glucose and lipid metabolism and bile acid metabolism disorders. Therefore, exogenous bile acid supplementation may be an effective way to solve the plant protein-induced NLD in Amur sturgeon. The regulation of bile acid on metabolism depends on its receptors. Our previous studies found that the bile acid receptor TGR5 was involved in the regulation of plant protein-induced NLD in Amur sturgeon. However, its responses to bile acid and regulatory mechanisms in NLD are not yet clear in fish. Therefore, this study aims to investigate the regulatory mechanism of TGR5 in the development of NLD and targeted intervention of bile acid by the combination of technological means in biochemistry, molecular biology, cell biology, pharmacology. This study will provide important references for the efficient use of plant proteins in carnivorous fish and the treatment of NLD in other fish species.