CD147分子在肝纤维化进展过程中的作用及分子机制研究

the patients'state of health is seriously affected by liver fibrosis and its complications.A number of experimental research have confirmed that the formation of new blood vessels intrahepatic and the activation of hepatic stellate cell play a vital role in the development of live fibrosis after the liver was damaged.However,the specific molecular mechanism in this process need further to be clearified. Our initial experimental results have demonstrated that the expression level of CD147 on hepatocellular membrane is significantly associated with the stage of hepatic fibrosis.We have also verified its important role in the formation of angiogenesis by activation of human umbilical vein endothelial cells.Thus, through interfering the expression level of CD147 both in vitro cell model and in vivo rat fibrotic model, this project aims to clearify the molecular mechanism of CD147 invovled in the activation of hepatic stellate cell and reconstruction of sinusodial vascularization, which are the two vital pathological processes of liver fibrosis progression, and then to provide new theoretical basis and specific treatment target for futher treatment strategy research of liver fibrosis .

肝纤维化及其并发症严重影响患者的生活质量及生命安全。国内外大量的实验研究表明肝损伤后静止状态的肝星状细胞被激活并转化成成纤维样细胞及肝脏内部新生血管的形成在肝纤维化的发生发展过程中扮起着重要甚至决定性的作用，但其具体的分子机制目前并没有彻底阐明。我们前期的实验研究结果显示：CD147在肝纤维组织中的表达水平和肝纤维化的发展阶段有着显著的相关性；同时还发现CD147具有促进人脐静脉内皮细胞活化并增强其新生血管形成的能力。基于此，本项目拟利用CD147基因干涉的体外细胞模型及体内大鼠肝纤维化模型，从肝星状细胞的活化以及肝内血管新生两方面探讨CD147分子通过参与上述两个方面的病理过程在肝纤维化发展过程中的作用及其具体的分子机制，以期为今后肝纤维化治疗策略的研究提供理论依据和特异的治疗靶点。

肝纤维化及其并发症严重影响患者的生活质量及生命安全。国内外大量的实验研究表明肝损伤后肝星状细胞活化及肝脏新生血管的形成在肝纤维化的发生发展中起着着重要甚至决定性的作用，但其具体的分子机制并没有彻底阐明。本项目利用体内外实验研究结果显示在肝纤维化进程中，TGF-β1上调肝细胞及窦周内皮细胞中的CD147表达，上调表达的CD147通过PI3K/Akt通路促进肝细胞中VEGF-A及窦周内皮细胞中的VEGF-AR2的转录与表达，后两者结合后促进肝组织新生幼稚血管的形成，最终促进肝纤维化进展。该课题的实施补充了肝纤维化过程的分子机制，为今后肝纤维化防治提供了新的思路及实验数据。