重组腺病毒介导的抑制miR-31表达通过促进靶基因HIF1AN表达而抑制四氯化碳诱导的肝纤维化的进展

Hepatic fibrosis is the pathological process of excessive deposition of extracellular matrix in the liver.HSCs are generally considered to be the major extra cellular matrix producer which play a crucial role in the progression of hepatic fibrosis.Recently many researches found that miRNAs were closely associated with the hepatic fibrosis.It is likely that miRNAs will be a new effective method for the treatment of hepatic fibrosis.However，at present most of the researches still remain on the cell level in vitro,and there is a lack of enough experiments in the animal model in vivo.Thus, in order to better understand the applicance of miRNAs in hepatic fibrosis,our research team will further explore the role of miR-31 in the progression of hepatic fibrosis in the animal model in vivo based on the previous cell experiment in vitro.Our previous results showed that miR-31/HIF1AN played an important role in the process of TGF-β/smad signalling pathway-mediated HSC activation.Thus, this research plans to further test the the protective effect of the adenovirus-mediated inhibition of miR-31 in the carbon tetrachloride(CCL4) induced hepatic fibrosis animal model through intravenous administration.This study will explore the mechanism and therapeutic potential of miR-31 for the development of hepatic fibrosis in vivo experiment, and provide scientific theory evidence for the treatment of hepatic fibrosis using miRNA in the future.

肝纤维化是各种病因引起的细胞外基质在肝内过度沉积的病理过程，活化的肝星状细胞（HSC）是产生细胞外基质最主要的来源，是肝纤维化发生发展的关键。近年来研究发现miRNA与肝纤维化的发生发展密切相关，有望成为一种有效治疗肝纤维化的新方法。但是，目前绝大多数研究仍停留在体外细胞实验层面上，尚缺乏足够的体内动物研究。因此，为了更深入地了解miRNA在肝纤维化中的应用前景，本课题组拟在前期细胞实验的基础上，进一步探索miR-31在体内肝纤维化动物模型中的作用。课题组前期研究发现，miR-31/HIF1AN参与了TGF-β/smad通路诱导的HSC活化。本课题拟进一步构建腺病毒介导的miR-31抑制剂，以尾缘静脉注射的方法，干预四氯化碳（CCL4）诱导的小鼠肝纤维化的发生发展，探索miR-31在体内动物实验中抗肝纤维化的作用机制及治疗前景，为将来miRNA应用于肝纤维化的治疗提供科学的理论依据。