肾间质纤维化是各种肾脏疾病发展至终末期肾病的共同病理基础。近来国内外研究对肾小管上皮细胞间充质转分化（EMT）与肾间质纤维化的关系提出质疑。进一步探寻肾间质纤维化形成的机制及其有效干预措施已成为当前亟待解决的问题。本研究以肾间质纤维化发生的初始环节为切入点，围绕“凝血酶可通过激活PAR-1/NF-κB细胞信号转导通路介导肾间质纤维化早期炎症细胞浸润和致纤维化因子的释放”这一假说，结合中药提取物水蛭素能特异性结合凝血酶的特点，通过在体实验研究，利用病理学、分子生物学技术，对水蛭素干预后肾间质纤维化早期细胞信号转导通路相关的PAR-1, NF-κB等指标，肾间质促纤维化因子TGF-β1和炎症因子ICAM-1，MCP-1，及细胞表面标志物a-SMA，E-Cadherin的表达进行观察，探讨水蛭素对于肾间质纤维化早期细胞信号转导的干预效应，为研发抗肾间质纤维化新药提供新的干预靶点和实验根据。

Renal Interstitial Fibrosis(RIF)is final way of end stage renal disease. In the past, EMT was thought to be crucial in RIF. However, the existence of EMT has been questioned by lately research. To further explore the pathogenesis and intervention of RIF is a problem that needs to be solved. The research focuses on the the initial stage of RIF as a new intervention point. On the hypothesis of “thrombin activates PAR-1/NF-κB cellular signal transduction and mediates early interstitial inflammation and release of pro-fibrosis factors”, combining the fact that hirudin can specifically bind thrombin, the research explores the intervention mechanism of hirudin in early cellular signal transduction in vivo by observing and testing the expression of initial cellular signal transduction related indicators such as PAR-1 and NF-κB, pro-fibrosis factor TGF-β1, inflammation factors ICAM-1 and MCP-1, and cell surface makers a-SMA and E-Cadherin in a pathologic and molecular level, and thus provides a new intervention target spot and experiment basis for the research and development of anti-fobrosis medicine.