肝纤维化是慢性肝病过程中发生的过度创伤愈合应答引起的细胞外基质过度沉积。肝纤维化可进展为肝硬化甚至肝衰竭，是肝病患者预后和生存最重要的决定因素之一。肝纤维化的病因治疗固然重要，但不能完全替代抗纤维化治疗。目前国际上尚无公认有效的抗纤维化药物，寻找肝纤维化治疗新靶点具有重要的科学意义和应用前景。缺氧和缺氧诱导因子1α在肝纤维化中通过炎症反应和血管生成促进纤维化进展。von Hippel-Lindau基因最主要的功能是靶向缺氧诱导因子1α使其蛋白水解。本项目旨在揭示von Hippel-Lindau基因对肝纤维化的抑制作用，并对其机制进行探究。此外，本项目为肝纤维形成过程中缺氧诱导因子1α在非缺氧区域聚积提供一个新的理论支持，即缺氧诱导因子1α的聚积可归因于von Hippel-Lindau表达下降，完善了缺氧与肝纤维化恶性循环理论，为肝纤维化的机制和治疗研究提供一个新的靶点。

Liver fibrosis is an excessive wound healing response in chronic liver diseases and results in extracellular matrix excessively accumulating.Liver fibrosis can progress to liver cirrhosis or even liver failure,which is one of the most important determinant of prognosis and survival in patients with liver diseases.Although the causal treatment of liver fibrosis is prominent, it cannot take the place of anti-fibrotic treatment.Since there are no established effective anti-fibrotic drugs in the world,seeking new targets of anti-fibrosis therapy has critical scientific significance and application prospects.Hypoxia and hypoxia inducible factor 1αaggravate liver fibrosis by inflammation and angiogenesis. The main function of von Hippel-Lindau gene is targeting of hypoxia inducible factor for proteolytic degradation.The aim of this project is to identify the inhibitory effect and mechanism of von Hippel-Lindau gene in liver fibrosis.Meanwhile, this project will provide a new theory accounting for the accumulation of hypoxia inducible factor 1α in normoxia area during liver fibrogenesis, which is caused by,at least in part,the downregulation of von Hippel-Lindau.This will fulfill the theory of the vicious circle of hypoxia and liver fibrosis and shed new light on the research of mechanism and treatment of liver fibrosis.