肝星状细胞激活的分子机制与抗肝纤维化治疗

Molecular Mechanism of Hepatic Stellate Cell Activation and Strategies of Anti-fibrosis Therapy

肝星状细胞(HSC)激活是肝纤维化发生的中心环节,其激活过程可分为始动阶段(旁分泌刺激和转录调控因素启动级联瀑布式的细胞反应)和持续阶段(旁分泌或自分泌刺激和细胞外基质重建共同维持HSC活化的表型反应)。肝脏中多种细胞和细胞因子参与调节了HSC的激活过程。活化型HSC的表型变化主要包括细胞增殖、收缩和纤维形成等。抗肝纤维化治疗策略主要包括调控HSC活化增殖或促其凋亡、抑制胶原合成或促其降解、细胞因子治疗和间充质干细胞治疗等。

The activation of hepatic stellate cell has been considered as the key step of liver fibrosis, mainly classified as initiation phase （paracrine stimulation and transcriptional events initiating a cascade of cellular responses） and perpetuation （paracrine and autocrine cytokine activity and ECM remodeling sustaining the activated phenotype）. Multiple cells and cytokines in liver play vital roles in regulating stellate cell activation. Major phenotypic features of activated hepatic stellate cell activation include proliferation, contractility, fibrogenesis, matrix degradation, chemotaxis, white blood cell chemoattraction, retinoid loss and cytokine release. Currently antifibrotic therapy strategies mainly include regulating the activating process, proliferation and apoptosis of hepatic stellate cells, inhibiting collagen synthesis or promoting collagen degradation, gene therapy and infusion of mesenchymal stem cells.