血管紧张素Ⅱ（AngⅡ）和TGF-β1/Smad信号转导通路在肝纤维化形成中起重要作用，而肝星状细胞（HSC）活化增殖是肝纤维化发生的中心环节。糜酶是生成AngⅡ的另一途径，我们的前期研究发现糜酶抑制剂（Chy-I）可减轻肝纤维化大鼠肝组织α-SMA、I型胶原的表达，但其分子机制尚不清楚。因此本项目利用大鼠肝纤维化模型，首先观察Chy-I干预治疗中AngⅡ系统不同环节组分及TGF-β1/Smad信号分子的表达，探讨糜酶介导的肝纤维化病理过程中有无AngⅡ和TGF-β1/Smad两个信号途径的交叉，在此基础上利用培养的HSC，观察Chy-I是否通过阻断TGF-β1/Smad信号转导通路抑制HSC的增殖活化，以阐明Chy-I对血管紧张素Ⅱ介导的TGF-β1/Smad信号通路的作用靶点。探讨Chy-I抗肝纤维化过程中抑制HSC活化或增殖的作用及其分子机制，为抗纤维化治疗提供理论依据。

Angiotensin II (AngII) and TGF-1/Smad signal transduction pathways play an important role in the formation of hepatic fibrosis, and the hepatic stellate cells (HSC) activation and proliferation are the central link of hepatic fibrosis. Chymase is another way to generate AngII. Our preliminary data demonstrated that chymase inhibitor (Chy-I) reduced the expression of -SMA, type I collagen in rat liver fibrosis tissues, but the molecular mechanism remains unclear. In this study, using rat hepatic fibrosis model, we will first examine the expression of different pathway components of AngII and the molecules of TGF-1/Smad signaling pathway during the intervention of Chy-I. Next, we wll investigate the potential cross talk between AngII and TGF-1/Smad signaling pathways in the process of the chymase-mediated hepatic fibrosis. To clarify the targets of Chy-I on AngII-mediated TGF-1/Smad signaling pathway, based on above research, we will further explore whether Chy-1 inhibts the activation of HSC proliferation through blocking the AngII and TGF-1/Smad signaling pathway in cultured HSC. Finally, we will verify the molecular mechanisms of Chy-I on inhibition of the activation or proliferation of HSC in anti-hepatic fibrosis. Our results will provide a theoretical basis for future anti-fibrotic therapy.