miR-134/LIN28A介导NF-κB信号通路研究肝纤维化机制及狗肝菜多糖（DCP）干预

课题组前期研究证实DCP具有显著保肝和抗HF作用，在HF大鼠中发现，miR-134表达下降，而LIN28、NF-κB及下游基因TNF-α、IL-6等大量表达，DCP可调控以上指标改善HF。NF-κB是肝脏炎症反应的中心环节，LIN28A和miRNA 均可介导NF-κB调控肝脏炎症，且LIN28A与miRNA存在交互关系。因此，推测miRNA-134和LIN28A可能存在交互作用，并介导 NF-κB通路调控HF进程。为此，本研究通过体内外实验，应用siRNA、慢病毒载体、荧光素酶报告基因、免疫共沉淀及miR-134-/-、LIN28A-/-和NF-κB-/-基因敲除小鼠等方法，明确miR-134与LIN28A是否为防治HF的新靶标及二者的交互关系，以及二者能否、如何调控NF-κB通路，同时揭示DCP是否通过miR-134/LIN28A介导NF-κB通路抗HF，为防治HF提供新靶标和潜在药物。

Research group found that Dicliptera chinensis polysaccharides(DCP) had a great hepatoprotective and anti-fibrotic effect. The expression of miR-134 decreased, but the level of LIN28、NF-κB and downstream target genes TNF-α and IL-6 increased significantly, and DCP could regulate above indexes to anti-HF in rats with hepatic fibrosis(HF).NF-κB, which can be transcribed by LIN28A or miRNA, runs through the inflammatory response of liver. LIN28A interacts with miRNA.Therefore, there is likely to be an interactive relationship between miRNA-134 and LIN28A, which participate in HF by regulating NF-κB pathway.For this purpose, the current study apply siRNA, lentiviral vector, luciferase reporter gene assay, immunoprecipitation, miR-134-/-、 LIN28A-/- and NF-κB-/- knocked out mice et al to demonstrate whether miRNA-134 and LIN28A are new targets for prevention and treatment of HF and interact, and whether or how they control NF-κB pathway, and meanwhile to reveal whether DCP counteracts HF via miR-134/LIN28A - NF-κB pathway and provide new targets and potential drugs for prevention and treatment of HF.