The Molecular Regulation Of MiRNA In NAFLD

miRNA is a kind of non-coding small RNA molecule, usually contains 19-25 base. Research has shown that the miRNA is highly conservative, and frequently downregulated or overexpressed in a variety of diseases. At present many kinds of miRNA become prominent disease markers for diagnosis and prognosis. A number of miRNA have involved in regulating the development of fatty liver and liver fibrosis. Deep study of miRNA holds great potential in improving the diagnosis and treatment of liver diseases.We analyze the changes of miRNA associated with fatty liver and liver fibrosis and the related proteins to study the molecular mechanism of miRNA involved in fatty liver and liver fibrosis through cell models of the miRNA transfection in vitro and animal models transfection in vivo in this study. The high efficient miRNA transfection verified the feasibility of liposome as a carrier in the mice model.The activation of hepatic stellate cells (HSCs) is the main process of liver fibrosis. We find that the content of miR-15b improved greatly in the transfection of HSCs comparing with the activated HSCs through determining the content change of miR-15b and the Bcl-2 in activated HSCs (P< 0.05). The content of Bcl-2 mRNA is almost the same in two groups of cells, but the protein is significantly reduced. The result suggests that miR-15b can inhibit the expression of Bcl-2 mRNA, thus reduce the Bcl-2 and promot HSCs apoptosis to control liver fibrosis.The vitro fatty liver cell model and the fatty liver animal model showed that miR-130a is significantly lower and the content of fatty acid synthase (FAS) and its activation factor PPAR-y increase in fatty liver comparing with normal group (P< 0.05). When transferred to miR-130a, FAS mRNA level dropped significantly (P< 0.05) and PPAR-y mRNA basically remain unchanged, but its protein decreased. We speculate that miR-130a reduces the FAS mRNA and protein content to control the process of fatty liver by inhibiting PPAR-y mRNA translation and reducing its protein content. And the model animal result shows that miR-130a can relieve the effects of fatty liver in mice demonstratingthe feasibility of miRNA as small molecular nucleic acid drugs. Moreover, the successful transport of miRNA by the liposomes provides the experimental basis for optimizing the liver targeting liposome for the treatment of liver diseases and the development of more drugs.