研究发现乙醇抑制肝脏胰岛素信号通路导致糖脂代谢紊乱是酒精性肝病(ALD)发生发展的主要原因。预实验发现甲基阿魏酸(MFA)对PI3K-Akt通路和糖脂代谢相关蛋白调控能有效抑制ALD，其机制不清楚。ALD大鼠肝组织miRNA测序显示MFA能显著下调miR-378b表达。文献报道miR-378及其同源序列在不同环节对胰岛素信号传导和脂代谢关键基因有调控作用。本实验组推测MFA抗ALD机制可能与下调miR-378b表达，调控PI3K-Akt信号通路，改善糖脂代谢有关。本项目拟采用L-02细胞模型、NIAAA大鼠模型及miR-378b敲除或过表达小鼠模型,结合miR-378bmimic和inhibitor技术，p110αRNAi干扰和过表达技术，阐明MFA调控miR-378b-p110α-PI3K/Akt信号通路抗ALD的分子机制。该研究为新型抗ALD药物的发现与研究提供了新思路和新靶点。

Studies have found that the glucose and lipid metabolism disorder caused by ethanol inhibiting the hepatic insulin signaling pathway is the main reason for the development of alcoholic liver disease (ALD). In the pre-experiment, we were surprised to find that Methyl ferulic acid (MFA) modulated the PI3K-Akt signal pathway and some glucose-lipid metabolism-related proteins and can effectively against ALD in alcoholic-induced liver disease model. However, the underlying mechanism is not fully clear. The results of miRNA sequencing showed that MFA can downregulate the expression of miRNA-378b significantly. It has been reported in the literature that miR-378 and its homologous sequences regulate the key genes of insulin signaling and lipid metabolism in different aspects. MiR-378b can bind to p110α subunit directly, and downregulation of miRNA-378b can activate PI3K-Akt signal pathway . Therefore, MFA is most likely to be a good new potential drug for the treatment of ALD. This study intends to elucidate how MFA works on miR-378b-p110α-PI3K/Akt signal pathway and its molecular mechanisms by using L-02 cell model, NIAAA rat model and miR-378 knockout or overexpressed mouse model , combining with the miR-378b mimic and inhibitor, p110α RNAi interference and overexpression. It is very profound for clearly explaining the pathogenesis of ALD and understanding the mechanism of the effect of MFA on ALD.The study provides new ideas and new targets for the discovery and research of new anti-ALD drugs.