壮药狗肝菜多糖（DCP）对肝纤维化TGF-β1/smad与p38MAPK信号通路的干预作用及其分子机制研究

TGF-β1/smad和p38MAPK信号通路与肝纤维化发病密切相关。壮药狗肝菜在民间防治肝病方面有独到疗效，课题组前期发现狗肝菜多糖（DCP）能有效抑制二甲基亚硝胺（DMN）致大鼠的肝纤维化、并且抑制了TGF-β1的表达和p38MAPK的磷酸化水平。为深入研究DCP抗肝纤维化的具体分子机制及干预靶点，本课题在成功建立DMN致大鼠纤维化模型的基础上，研究DCP对TGF-β1/smad与p38MAPK 信号通路的作用及其对肝细胞增殖和活化状态的影响；同时研究DCP对大鼠HSC-T6肝星状细胞的抑制作用，并检测其对TGF-β1/ smad与p38MAPK 通路的影响，以及基于靶蛋白转录辅激活因子（p300/CBP）探讨两个通路之间可能存在的交互作用点，进一步明确DCP抗肝纤维化的分子机制，为其肝纤维化治疗的临床应用提供实验及理论依据。

Study of TGF-β1/smad and p38MAPK signaling pathways is etiological target of hepatofibrosis. And the targeted medication research associated with the pathways on liver fibrosis contributes to inhibiting fibrotic development. Notably, ethnopharmacology-derived Dicliptera chinensis has reported to effectively reverse fibrotic process of liver tissue in folk. In addition, our previous studies found that Dicliptera chinensis polysaccharides (DCP) resulted in attenuation of hepatofibrosis, inhibition of both TGF-β1 expression and p38MAPK phosphorylation. To further investigating the DCP anti-fibrotic effect involved in exact molecular mechanisms and intervention targets. This study first employs the DMN-induced liver fibrosis in rats to observe the effect of DCP on TGF-β1/smad and p38MAPK signaling pathways and the impact on proliferation and activation in hepatocytes. In addition, we also evaluate DCP-mediated inhibitory effect involved in proliferation and activation in HSC-T6 cell strain, and detection of its impact on TGF-β1 / smad and p38MAPK pathways, as well as the possible interaction targeted p300/CBP between these two pathways. Taken together, we aim to further identify the molecular mechanism of DCP-mediated anti-fibrotic effect and to provide the experimental and theoretical basis for its clinical application.