非酒精性脂肪性肝炎（NASH）是慢性肝病的主要病因，可发展为肝硬化、肝癌，而其发病机制至今仍不完全明确，且治疗手段有限。我们在前期研究中发现，活性维生素D3（VD3）抑制胆碱缺乏饮食诱导的大鼠NASH脂质过氧化和炎症。最近报道花生四烯酸（AA）网络调节在NASH发病机制中具有重要的作用，与其代谢诱导脂质过氧化和炎症反应有关。我们在预实验中发现，该模型肝脏中与n-6多不饱和脂肪酸（PUFA）—AA代谢通路，如磷脂酶A2（PLA2）/AA途径相关基因差异表达，活性VD3对此有明显抑制作用，提示：胆碱缺乏和n-6 PUFA可能有交互作用、VD3可能通过调控PLA2/AA代谢网络来改善脂质过氧化与抑制炎症。因此，本项目拟建立此NASH模型，阐明胆碱缺乏和n-6 PUFA的关系以及PLA2/AA途径在NASH发展中的机制和VD3在其中的作用机制，为NASH发病机制及防治提供理论依据与可能的有效途径。

Non-alcoholic steatohepatitis (NASH) is the main cause of chronic liver disease, with likely progression to cirrhosis and hepatocellular carcinoma. Its pathogenesis is still not completely clear, and the therapy is limited. We recently reported that 1,25(OH)2D3 supplementation ameliorated NASH lipid peroxidation and inflammation in the liver in the choline-deficient diet -induced NASH model. Studies showed that AA of regulatory network plays an essential role in the pathogenesis of NASH due to lipid peroxidation and inflammatory response induced by its metabolism. Thereafter, in this model, we further observed that the differentially expressed genes associated with phospholipase A2(PLA2)/ arachidonic acid (AA) pathway in the n-6 polyunsaturated fatty acids (PUFA)- AA metabolic pathway and which were altered upon 1,25(OH)2D3 treatment in the liver on the gene microarray analysis and real-time fluorescence quantitative PCR by the pre-experiment. The results suggested that there may be an interaction between choline-deficient and n-6 PUFA, and 1,25(OH)2D3 may improve NASH lipid peroxidation and inflammatory in the liver through PLA2 / AA pathway. Therefore, in this study, to explore the relationship between the n-6 PUFA and the choline- deficient, and the mechanism of PLA2 / AA pathway in the development of NASH, and the mechanism for 1,25(OH)2D3 to ameliorate NASH. Our study may lead to understanding pathogenesis and provide a promising approach to prevent and treat NASH.