肝纤维化发生发展的信号通道及其相关靶点治疗进展

Therapeutic Advances in Signaling Channels and Their Associated Targets in the Development of Liver Fibrosis

摘要: 肝纤维化是由多种病因引起的肝细胞反复损伤与修复、细胞外基质异常增生的病理过程，是进展为肝硬化甚至肝癌的关键因素。尽管去除病因可在一定程度上逆转肝纤维化，但逆转往往出现得较慢或较少，无法避免病情的进展，尤其是在肝纤维化晚期阶段。因此，明确肝纤维化的发生机制，探索逆转肝纤维化的治疗靶点是现阶段的重要研究方向。截至目前，已有大量抗纤维化方法在细胞研究和动物模型中得到验证，而且，越来越多的分子也正在以及将要进入临床试验，这推动了旨在寻找新治疗方法的前临床研究和临床试验。在本综述中，我们总结了肝纤维化发生发展的分子机制，以及基于这些分子机制潜在的治疗方法。

Abstract: Liver fibrosis is a pathological process of repeated damage and repair of hepatocytes and abnormal proliferation of extracellular matrix caused by a variety of etiologic factors, and is a key factor in the progression to cirrhosis and even hepatocellular carcinoma. Although removing the causes can reverse liver fibrosis to a certain extent, the reversal often occurs slower or less frequently, and the progression of the disease cannot be avoided, especially in the advanced stage of liver fibrosis. Therefore, clarifying the mechanism of liver fibrosis and exploring therapeutic targets for reversing liver fibrosis are important research directions at this stage. To date, a large number of antifibrotic approaches have been validated in cellular studies and animal models, and an increasing number of molecules are and will be entering clinical trials, which is driving preclinical studies and clinical trials aimed at finding new therapeutic approaches. In this review, we summarize the molecular mechanisms involved in the development of liver fibrosis and the potential therapeutic approaches based on these molecular mechanisms.