非酒精性脂肪性肝病（NAFLD）已成为我国最为常见的慢性肝病之一。迄今该病确切发病机制仍未阐明，也缺乏公认、有效的治疗方法。脂质介质Protectin DX（PDX）是二十二碳六烯酸（DHA）经过脂氧合酶催化作用合成的衍生物。我们的前期研究发现，高脂饮食小鼠予PDX干预后肝脏脂质沉积减轻，提示PDX对NAFLD具有保护作用。同时我们发现PDX干预后肝脏AMPK激活，已有研究证实AMPK的激活可通过多种信号途径改善NAFLD，故本项目拟开展以下工作：1、在不同的NAFLD小鼠模型中，明确PDX对肝脂肪变性及脂肪性肝炎形成的影响；2、通过体内外实验明确AMPK信号通路在PDX调控肝脏脂质代谢、炎症反应中的作用及机制；3、进一步明确AMPK-mTOR通路相关的细胞自噬在PDX调控NAFLD形成中的作用及分子机制。通过该项目希望能为NAFLD的药物干预治疗提供新思路。

Nonalcoholic fatty liver disease (NAFLD) has been one of the most common causes of chronic liver diseases in China. However, its exact pathogenesis remains unclear and there has been no effective pharmacological therapy. Protectin DX (PDX) is produced by the sequential lipoxygenation of docosahexaenoic acid (DHA). In our previous study, we found that administration of PDX to high fat diet (HFD)-fed mice resulted in reduced hepatic triglyceride contents and increased hepatic AMPK phosphorylation which suggested the protection effect of PDX on NAFLD. Moreover, accumulating evidence shows that AMPK activation may reduce NAFLD by several mechanisms. Therefore, to confirm the effects of PDX on the progression of NAFLD, we will further focus on: 1) The role of PDX in regulating hepatic steatosis and steatohepatitis in different animal models. 2) Whether PDX regulates NAFLD by AMPK activation in in vivo and in vitro studies. 3) Whether PDX improves NAFLD by inducing autophagy through AMPK-mTOR signal pathway. This study will provide a promising approach for the treatment of NAFLD.