目前，非酒精性脂肪肝(NAFLD)已成为一个公共健康问题，且尚无理想的治疗药物。泽泻醇B-23-乙酸酯(AB23A)是一种天然三萜类化合物，具有一定的保肝及肠道屏障保护作用。前期的蛋白组学研究结果发现护肝清脂片防治NAFLD与微生物在不同环境中的代谢及肠道屏障功能密切相关。而AB23A作为其主要代谢产物之一，可能发挥了重要的作用。相关研究表明肠道屏障损伤是导致NAFLD的一个重要因素，LPS/TLR4的激活所造成的Nox1高表达及后续的ROS产生是其中的关键环节。另一方面，肠道中FXR受体的激活能阻止肠道屏障通透性增加。因此，本项目拟通过建立高脂饮食诱导的NAFLD小鼠模型以及体外培养Caco-2细胞并结合相关分子生物学方法探讨LPS/TLR4-Nox1/ROS信号通路是肠道屏障损伤导致NAFLD的关键环节及AB23A的可能作用机制和靶点，为AB23A治疗NAFLD提供更多的基础理论依据。

Currently, non-alcoholic fatty liver disease (NAFLD) has become a public health problem with no ideal treatment. Alisol B-23-acetate (AB23A) is a natural triterpenoid compound with a certain protective effect of protecting liver and intestinal barrier. Early proteomics research results showed that the anti- NAFLD effects of Hugan Qingzhi is associated with microbial metabolism in diverse environments and gut barrier function. AB23A, as a major metabolite of Hugan Qinzhi, may play an important role in the process. Several researches showed that gut barrier injury is an important factor in NAFLD. High expression level of Nox1 and subsequent ROS generation caused by the activation of LPS/TLR4 are a key point in the process. On the other hand, the activation of the FXR receptor in the intestinal tract can inhibit the permeability of the intestinal barrier. Thus, this study proposed to clarify LPS/TLR4-Nox1/ROS axis and mechanisms of AB23A's effects in gut barrier injury-induced non-alcoholic fatty liver disease by establishing a high fat diet-induced NAFLD mouse and culturing Caco-2 in vitro, thereby to provide more basic theoretical basis for AB23A in the treatment of NAFLD.