甲基阿魏酸调控LINC00657与miR378b-CAMKK2-AMPK的交互作用改善脂代谢抗ALD的机制研究

乙醇代谢物抑制磷酸腺苷依赖的蛋白激酶（AMPK）活性引发肝脂质代谢紊乱是酒精性肝病 (ALD)发生的主要原因。前期研究发现甲基阿魏酸（MFA）激活AMPK、FoxO1通路能有效抑制ALD，但机制不清。NIAAA大鼠模型肝组织miRNA测序发现MFA能显著下调miR-378b表达。数据库分析显示miR-378b与AMPK通路激活的重要因子CAMKK2 mRNA在3’-UTR有应答原件；LINC00657是miR-378b的竞争性内源RNA。本课题组创新性提出基于LINC00657与miR378b-CAMKK2-AMPK的交互研究MFA调控肝脏脂质代谢抗ALD的研究构想。本研究拟采用L-02细胞模型，NIAAA大鼠模型，结合基因沉默与过表达技术，研究LINC00657与miR-378b交互对CAMKK2-AMPK通路传导的影响及MFA的调控机制，为新型抗ALD药物的发现与研究提供新思路和新靶点

Alcohol metabolites inhibit adenosine phosphate-dependent protein kinase (AMPK) activity and lead to liver lipid metabolism disorder, which is the main cause of alcoholic liver disease (ALD). Previous studies have found that methyl ferulic acid (MFA) can effectively inhibit ALD by regulating AMPK and FoxO1 pathways, but the underlying mechanism is unclear. MiRNA sequencing of liver tissue in NIAAA rat model found that MFA significantly down regulated miR-378b expression. The database analysis showed that miR-378b and CAMKK2 mRNA, an important activator of AMPK, have a response element in 3'-UTR; LINC00657 is a competitive endogenous RNA of miR-378b. based on literature analysis and bioinformatics Analysis，The research group innovatively proposed the research concept of MFA regulating liver lipid metabolism against ALD based on the interaction between LINC00657 and miR378b-CAMKK2-AMPK. This research intends to study the effect of LINC00657 and miR-378b interaction on the conduction of CAMKK2-AMPK pathway and the regulation mechanism of MFA by using the L-02 cell model, NIAAA rat model and gene silencing and overexpression technology. This experiment will provide new ideas and new targets for the discovery and research of new anti-ALD drugs.