肾素血管紧张素系统与肝纤维化的发生和发展

Rennin angiotensin system and the occurrence and development of liver fibrosis

肝纤维化是各种因素引起细胞外基质的生成和降解失衡,最终导致肝组织重塑。肾素血管紧张素系统(rennin angiotensin system,RAS)是机体内重要的内分泌调节系统,参与机体血压调节、水盐代谢等平衡并且发挥不可替代的作用。近些年的研究发现,肝脏中也存在局部完整的RAS,而肝纤维化的发生与肝组织RAS有着不可分割的关系。以前大量研究已经证实,RAS经典轴ACE-AngⅡ-AT1R在肝纤维化中表达上调,而抑制该轴的表达可以改善肝纤维化,也有研究表明,RAS非经典轴ACE2-Ang(1-7)-MasR通过拮抗经典轴而起到改善肝纤维化的作用;同时,RAS相关药物(经典轴抑制剂和非经典轴激动剂)显示出抗肝纤维化治疗的巨大潜力。该文就近年来对RAS在肝纤维化发生发展过程中的作用及其相关药物对肝纤维化的治疗作用予以综述。

Liver fibrosis is caused by various factors causing the formation and degradation of extracellular matrix imbalance,ultimately leading to liver tissue remodeling.Renin angiotensin system(RAS)is an important endocrine regulatory system in the body,and plays an irreplaceable role in blood pressure regulation,water and salt metabolism and other balance.Recent studies have found that there is also a local complete RAS in the liver,and the occurrence of liver fibrosis has an inseparable relationship with liver tissue RAS.A large number of previous studies have confirmed that the expression of ACE-AngⅡ-AT1R,the classical axis of RAS,is up-regulated in liver fibrosis,and inhibiting the expression of this axis can improve liver fibrosis.Studies have also shown that the RAS non-classical axis ACE2-Ang(1-7)-MasR can improve liver fibrosis by antagonizing the classical axis.At the same time,RAS-related drugs(classical axis inhibitors and non-classical axis agonists)show great potential for anti-hepatic fibrosis therapy.In this paper,the role of RAS in the occurrence and development of liver fibrosis and the therapeutic effects of its related drugs on liver fibrosis were reviewed.