非酒精性脂肪肝（NAFLD）已成为全球性的公共健康问题，迄今为止其发病机制尚未阐明，亦没有理想的治疗药物。最新研究表明BNip3介导的线粒体自噬（mitophagy）异常能够导致肝脏脂质代谢紊乱，但其细胞内信号转导机制仍未清楚。本课题组前期研究发现木通皂苷D能够激活BNip3，提高自噬水平、保护线粒体，降低肝脏脂质沉积。由此推测木通皂苷D抗NAFLD的作用可能是通过调控BNip3-mitophagy相关通路实现的。本研究拟采用油酸诱导肝细胞脂质沉积及ob/ob小鼠为模型，研究干预BNip3及其上游AMPK、PI3K/AKT信号通路对线粒体自噬的影响，探讨木通皂苷D是否通过激活BNip3-mitophagy通路而实现调控NAFLD肝脏脂质代谢紊乱的作用，阐明其信号转导机制，为开发针对BNip3-mitophagy通路的药物提供新的思路，也为木通皂苷D的临床应用提供理论和实验依据。

Non-alcoholic fatty liver disease (NAFLD) has became a global public health issue, however the exact pathogenesis has not been elucidated and there is no ideal drugs for NAFLD. Recent studies have shown that BNip3-mediated mitophagy played critical roles in the hepatic lipid metabolism, however the related mechanims of the cell signaling transduction still unknown. In the preliminary studies we have found that Akebia saponin D (ASD)could activate BNip3, improve the level of autophagy, protect mitochondrial and reduce liver lipid deposition.The significant anti-NAFLD effects of ASD may be associated with the BNip3-mitophagy signaling pathway. The project intends to predict the drug target of ASD by using oleate induced hepatic steatosis and ob/ob mice, and investigate the effect of mitophagy by interfere BNip3 and AMPK、PI3K/AKT signaling pathways. The relationship between BNip3-mitophagy and NAFLD will be studied. These researches might provide a new target, a potential drug for the treatment of NAFLD, and provide new ideas for prevention and treatment of NAFLD.