mirna对非酒精性脂肪肝病变的分子调控作用制药工程专业论文.docxVIP

北京化工大学硕士学位论文比较脂肪肝中miR．130a会出现明显下调(PO．05)，脂肪酸合成酶 北京化工大学硕士学位论文 比较脂肪肝中miR．130a会出现明显下调(PO．05)，脂肪酸合成酶 (FAS)及其激活因子PPAR吖含量增多。当转入miR．130a后，FAS 的mRNA水平显著下降(P0．05)，而PPAR吖的mRNA含量基本 不变，但其蛋白有所减少。推测miR-130a通过抑制PPAR吖的mRNA 的翻译，减少其蛋白质含量，进而使FAS的mRNA和蛋白含量下调， 对脂肪肝过程进行调控。并且动物实验结果表明，miR-130a对于小 鼠的脂肪肝具有缓解治疗作用，为miRNA作为小分子核酸药物的可 行性提供支持。开创了脂质体载体肝靶向运输miRNA的新方法。同 时，脂质体载体肝脏靶向运输miRNA的成功也为进一步优化肝靶向 脂质体，使其可以用于更多肝脏疾病的治疗和药物开发提供了实验依 据。 关键词：脂肪肝，肝纤维化，miRNA，脂质体载体，转染 万方数据 ABSTRACITHE ABSTRACI THE MOLECULAR REGULATION OF miRNA IN NAFLD ABSTRACT miRNA is a kind of non-coding small RNA molecule，usually contains 1 9—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 1iver 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-1 5b improved greatly in the transfection of HSCs comparing with the activated HSCs through 万方数据 北京化工大学硕士学位论文determining 北京化工大学硕士学位论文 determining the content change of miR-1 5b and the Bcl一2 in activated HSCs fPO．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-1 5b can inhibit the expression of Bcl一2 mRNA，thus reduce the Bcl-2 and promot HSCs apoptosis to control liver fib