miR-152通过调节Wnt信号通路致非酒精性脂肪肝病的机制研究

肝细胞内脂质异常积聚是非酒精性脂肪肝病（NAFLD）的重要病理学基础，但其机制不明。前期研究中，我们通过二代测序技术发现miR-152差异高表达于NAFLD大鼠肝组织中；生物信息学发现，miR-152在人与大鼠间高度保守，Wnt10b是其靶基因；预实验发现在肝细胞中过表达人miR-152不但显著促进脂质积聚，而且显著下调Wnt10b，提示miR-152可能通过调节Wnt信号通路的机制致肝细胞内脂质积聚。本研究拟阐明miR-152的生物学特征；采用miRNA mimics及inhibitors评价miR-152对NAFLD细胞脂质合成、Wnt信号通路的影响；以Wnt信号通路为切入点，分析miR-152影响脂质合成的机制，论证miR-152在NAFLD中的作用与机制。miR-152影响NAFLD脂质合成的作用与机制均未见报道，本研究具有源头创新性，可为儿童NAFLD的防治提供新靶标。

Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides, which are formed from the esterification of FFA and glycerol within hepatocytes. Although nowdays the "three hit hypothesis" was considered as the dominant theory, the pathogenesis of NAFLD is still vague and needs further exploration. In our previous study, we found that miR-152 was highly expressed in NAFLD rat liver tissue by deep sequencing technology. We also found that miR-152 was highly conserved between human and rats, and Wnt10b was the target gene through bioinformatics software and database analysis. Further preliminary experiments disclosed that over-expression of miR-152 in human hepatocyte not only significantly promoted lipid accumulation but also dramatically down-regulated Wnt10b, which indicated that miR-152 may induce lipid accumulation in hepatocyte through the mechanism of regulation of Wnt signal pathway. This study is to elucidate the biological characteristics of the miR-152 and its effect in the hepatocyte lipid synthesis and in the Wnt signal pathway by overexpression and knockdown miR-152 in L-02 hepatocytes. We also intend to investigate the function and mechanism of miR-152 in NAFLD by looking at the starting point of Wnt signal pathway. So far, the role and mechanism of the miR-152 in NAFLD lipid synthesis has not been reported, thus this study is initially innovation. It may provide new targets for the prevention and treatment of children of NAFLD.