膈下逐瘀汤调节内皮祖细胞构建肝纤维化微环境的机制研究

Pathologic liver blood sinus endothelial and extracellular matrix formation are main factors in influencing the prognosis of liver fibrosis, and special micro environment of liver fibrosis (angiogenesis, cell factor and immune response) through a variety of regulatory mechanisms affect its prognosis. Our preliminary results show that: the endothelial progenitor cells (EPCs) homing and enrichment of liver fibrosis tissues indicate that EPCs may play an important role in the microenvironment. Traditional Chinese medicine has certain curative effect in the treatment of liver fibrosis;Studies found the Gexiazhuyutang can significantly improve liver fibrosis and participate in the remodeling of blood vessel of liver inside and outside, relating to improve the hepatic microcirculation closely, but the adjustment mechanism is unclear.We propose that: Gexiazhuyutang can regulate the EPCs in constructing microenvironment of liver fibrosis, reversing or slowing down liver fibrosis to some extent.To test this hypothesis, we used animal model of hepatic fibrosis to reconstruct the bone marrow and other methods, 1, to assess that aggregation and the proliferation phase research of EPCs to the cirrhosis of the liver tissue under the drug intervention;2, to the evaluate that EPCs play a role of angiogenesis in liver fibrosis organization under the drug intervention;3, to screen and determine the key protein of EPCs, secreting and regulating angiogenesis in cirrhosis of the liver tissue. This study will provide some ideas and theory basis about anti fibrosis treatment of liver.

病理性肝血窦内皮化和细胞外基质生成是影响肝纤维化预后的主要因素，而肝纤维化特殊的微环境（血管新生、细胞因子和免疫反应）通过多种调节机制影响其预后。我们的前期实验表明：内皮祖细胞(EPCs)归巢并富集肝纤维化组织内，这些结果提示EPCs可能在这微环境中扮演重要角色。中医中药在治疗肝纤维化有一定疗效；研究发现膈下逐瘀汤能明显改善肝纤维化且参与重塑肝内外血管，与改善肝脏微循环密切相关，但对其调节机制尚不明确。我们假设：膈下逐瘀汤调节的EPCs参与构建肝纤维化微环境，能在一定程度上延缓或逆转肝纤维化。为证实这一假设，我们采用骨髓重构的肝纤维化动物模型等方法，1，评估药物干预时EPCs向肝硬化组织聚集和增殖的时相研究；2，评估药物干预时EPCs在肝纤维化组织中血管新生的作用；3，筛选并确定EPCs分泌与调节肝硬化组织中血管新生的关键蛋白。本研究将为肝纤维化的诊治提供又一思路和和理论依据。