肝星状细胞与肝纤维化及其逆转的研究进展

Advances in Hepatic Stellate Cells and Hepatic Fibrosis and Its Reverse

摘要: 肝纤维化是肝硬化进展的早期步骤，感染、毒性/药物诱导，代谢和自身免疫都可以导致肝纤维化。而在肝纤维化的过程中，肝星状细胞(hepatic stellate cells, HSCs)发挥着关键作用，活化的肝星状细胞是肝纤维化时过量细胞外基质的主要来源，通过TGFβ-Smad信号通路、PDGF信号通路、NF-κB信号通路等激活静息状态的肝星状细胞，激活的HSCs (activated hepatic stellate cells, aHSCs)大量增殖发生表型改变并分泌过多的细胞外基质沉积于肝脏。传统观点认为肝硬化是不可逆的疾病，然而最近的证据表明，通过抑制HSCs的活化和增殖，免疫清除、细胞凋亡衰老等机制参与活化HSCs的清除以促进肝纤维化的逆转。并将HSCs作为肝纤维化治疗的靶点，研究发现无论是天然提取物或是合成化合物，都具有一定的抗纤维化作用。本文将对肝星状细胞与肝纤维化及其逆转的相关关系，以及与HSCs相关的肝纤维化治疗的研究进展进行简要综述。

Abstract: Liver fibrosis is an early step in the progression of cirrhosis. It can be caused by infection, toxicity/drug induction, metabolism and autoimmunity. In the process of liver fibrosis, hepatic stellate cells play a key role and are the main source of excessive extracellular matrix during liver fibrosis. Through TGFβ-Smad, PDGF, NF-κB and other signal pathways, the activated hepatic stellate cells proliferate and secrete excessive extracellular matrix which deposits in the liver. The traditional view is that cirrhosis is an irreversible disease. However, recent evidence suggests that mechanisms such as inhibiting the activation and proliferation of HSCs, immune clearance, apoptosis and senescence are involved in the clearance of activated HSCs to promote the reversal of liver fibrosis. HSCs were used as the therapeutic target for liver fibrosis. It is found that both natural product extract and synthetic compound have certain anti-fibrosis effect. Here we briefly review the correlation between hepatic stellate cells and hepatic fibrosis and its reversal, as well as the research progress in the treatment of hepatic fibrosis related to HSCs.