非酒精性脂肪肝病（NAFLD）是全球最常见的慢性肝脏疾病之一，常与肥胖和2型糖尿病等代谢性疾病相联系，可发展为肝硬化和肝癌。NAFLD发病率在世界范围不断上升，且缺乏有效的治疗药物，已成为危害公共健康的一大问题。本课题组前期的模型优化初步研究发现，阴沟肠杆菌（E.cloacae）促进了高脂饲喂小鼠NAFLD的发展，并引起自噬和Toll样受体（TLR）及相关信号通路的变化，但其作用机制还有待深入研究。本项目拟在前期工作基础上，应用分子生物学和细胞生物学等技术，通过建立体内外NAFLD研究模型，分析TLR对E.cloacae诱导的NAFLD发生发展的影响；通过自噬和TLR通路的关键信号分子靶向研究，深入探讨TLR信号通路介导的自噬在NAFLD炎症中的分子机制，可为筛选治疗NAFLD的作用靶点提供参考，同时为NAFLD及相关代谢性疾病的发病机制和治疗研究提供理论指导和实验依据。

Nonalcoholic fatty liver disease(NAFLD), which is associated with obesity, type 2 diabetes and other metabolic disease, is one of the most common chronic liver diseases around the world and may further develop into liver cirrhosis and liver cancer. At present, NAFLD has become a major public health hazard due to the globally increasing morbidity and lack of effective therapeutic drugs. During the preliminary study on optimization of animal model, it was found that E.cloacae promoted the development of NAFLD in mice fed with high fat diet, further induced autophagy and activated toll-like receptor (TLR) and related signaling pathways, but its mechanism of action still needs to be deeply studied. Based on our previous work, this project intends to use molecular biology, cell biology and other technologies to analyze the effect of TLR on the occurrence and development of NAFLD induced by E.cloacae through establishing NAFLD model in vivo and in vitro. Through molecular targeted research studies on key signaling molecules of autophagy and TLR signaling pathway, the molecular mechanism of TLR-mediated autophagy on inflammation of NAFLD will be further explored. The study may not only provide reference for the screening of targets for NAFLD, but also offer new theoretical guidance and experimental basis for the research of pathogenesis and treatment of NAFLD and related metabolic diseases.