SWAP70在非酒精性脂肪肝病中的作用及机制研究

非酒精性脂肪肝病（NAFLD）现已超越病毒性肝炎成为我国居民第一大肝脏疾病，然而目前却无有效临床药物。炎症反应是NAFLD发生发展过程中的一项极为关键的病理特征和调控因素，鸟苷酸交换因子SWAP70参与多项免疫炎症信号的调控，但其在NAFLD中的作用尚未见报道。我们的研究表明，SWAP70在NAFLD小鼠肝脏中的表达量显著降低，且SWAP70基因敲除显著加剧NAFLD进程，表明SWAP70在NAFLD病理过程中起着非常关键的调控作用。本项目拟进一步利用NAFLD小鼠及细胞模型，明确SWAP70在NAFLD中的作用，并结合互作组学和RNA-seq等手段，深入探讨SWAP70参与NAFLD调控的具体分子机制，拓展人们对NAFLD病理机制及SWAP70蛋白功能的认识。同时，本项目还将进一步评估SWAP70及其下游靶蛋白对NAFLD小鼠模型的逆转效果，期望为NAFLD疾病的治疗提供新靶点和新策略。

Non-alcoholic fatty liver disease (NAFLD) has now become the major liver disease in our country, with a larger population than viral hepatitis. However, there is no effective clinical drug currently. Inflammation is an extremely critical pathological feature and regulatory factor in the development of NAFLD. The switch-associated protein SWAP70 is involved in the regulation of multiple immune inflammation signals, but its role in NAFLD has not been reported. Our research shows that the expression level of SWAP70 in the liver of NAFLD mice is significantly reduced, and the SWAP70 gene knockout significantly aggravates the NAFLD process, indicating that SWAP70 plays a key regulatory role in the pathological process of NAFLD. This project intends to identify the role of SWAP70 in NAFLD by using the NAFLD mouse and cell model, and expound the specific molecular mechanism of SWAP70 involved in the regulation of NAFLD by employing the interaction proteomics and RNA-seq. This will expand our understanding for the pathological mechanism of NAFLD and the function of SWAP70 protein. At the same time, this project will further evaluate the therapy effect of SWAP70 and its downstream target proteins on the NAFLD mouse model, looking forward to provide new targets and new strategies for the treatment of NAFLD diseases.