肝纤维化的逆转机制

Reversal mechanism of hepatic fibrosis

越来越多的临床证据表明, 肝纤维化与一定程度的肝硬化均可发生肝组织学的逆转与预后改善。肝纤维化涉及多种细胞与多个环节, 其逆转机制也十分复杂, 主要有肝细胞炎症坏死减轻与肝细胞再生、活化肝星状细胞的凋亡与失活、肝窦内皮细胞与微血管的改善、肝巨噬细胞恢复型极化等, 且细胞之间相互影响。而基质金属蛋白酶抑制因子表达减少、基质金属蛋白酶活性增加、细胞外基质降解增多则是肝纤维化逆转的生化学基础。但是, 目前肝纤维化逆转的临床病理机制研究较少, 不同病因不同程度肝纤维化逆转的关键靶点群尚不清楚, 缺乏相应的转化应用研究。深入系统地了解肝纤维化逆转的特点与机制, 不仅可丰富对肝纤维化肝硬化自然史的认识, 亦可为抗肝纤维化的治疗药物研发及其临床应用提供参考帮助。

There is an increasing histological clinical evidence that both hepatic fibrosis and some degree of cirrhosis reversal can improve prognosis.Hepatic fibrosis involves a variety of cells and steps,and its reversal mechanism is also very complex,mainly including the reduction of hepatocyte necrosis and regeneration,the apoptosis and inactivation of activated hepatic stellate cells,and the reversal of hepatic sinusoidal endothelial cells and microvessels,restorative hepatic macrophages polarization and cell-to-cell interactions.Furthermore,the biochemical basis for reversal of hepatic fibrosis is decreased expression of matrix metalloproteinase inhibitors,up-regulation of matrix metalloproteinase activity,and increased degradation of extracellular matrix.However,at present,there are few studies on the clinicopathological mechanism of liver fbrosis reversal,and the key target groups of different etiologies with different degrees are still unclear,and the corresponding translational application research is lacking.Therefore,an in-depth and systematic understanding of the characteristics and mechanisms of hepatic fibrosis reversal can not only enrich the understanding of the natural history of hepatic fibrosis and cirrhosis,but also provide reference for the development and clinical application of anti-hepatic fibrotic drugs.