肝硬化是消化化系统的常见疾病，合并的胆道动力异常可导致常见临床症状，并推动其病理生理过程。以往肝硬化时胆道动力的研究都主要集中在胆囊，关于Oddi括约肌（SO）功能障碍少有关注。我们前期研究发现，肝硬化时胆管黏膜屏障受损，改变成分的胆汁酸渗透至深部组织，SO所处微环境改变，可能造成其结构及功能异常，导致SO功能障碍。本项目拟通过形态学研究观察肝硬化时SO的组织病理改变；通过离体功能实验分析肝硬化时SO的功能状态及胆汁酸的调控作用；对胆汁酸膜受体TGR5进行检测并对其影响SO功能的相关机制进行分子机理研究。通过本项目的实施，拟探索肝硬化时是否存在SO组织病理改变及功能障碍；了解影响SO功能的主要胆汁酸；研究胆汁酸通过TGR5影响SO功能的调控机制，为药物或内镜改善肝硬化时SO功能障碍提供理论基础。

Cirrhosis is a common disease of digestive system. The accompanying dyskinesia of biliary tract can cause a series of symptoms and worsen the pathophysiological processes. Previous studies mainly focused on the dysmotility of gallbladder while little attention was paid to the dysfunction of sphincter of Oddi (SO). In our pilot studies, we observed the damages of bile duct epithelial tight junctions of cirrhotic animals. Thus, bile acids, of which the composition has changed can easily permeate to deeper tissues and change the micro-environment of SO, induce structural and functional abnormalities and finally lead to SO dysfunction. In this project, we plan to study the histopathological features of SO in cirrhosis; analyze the motility function of SO and the effect of bile acids in isolated SO in vitro; analyze the expression of bile acid membrane receptor TGR5 and its function on SO. Through this project, we will conduct a comprehensive research on the possible mechanism of SO dysfunction in cirrhosis, aiming to provide the theoretical basis on pharmacological and endoscopic intervention of SO dysfunction in cirrhotic patients.