肝纤维化治疗新策略

New strategy for the treatment of hepatic fibrosis

肝纤维化是各种慢性肝病共有的病理改变,逆转肝纤维化可阻止大多数慢性肝病进展。肝星状细胞(HSC)活化是肝纤维化发生的中心环节,故传统治疗策略大多以HSC为治疗靶点,并在动物实验取得良好疗效。但最近研究发现活化HSC也可促进肝细胞再生和肝脏损伤修复。肝细胞核因子是一组对肝细胞分化和功能维持起关键作用的转录因子,既可减少细胞外基质(ECM)分泌,又可促进肝细胞再生,保护肝细胞功能。促进肝细胞核因子表达是治疗肝纤维化更为理想的策略。

Hepatic fibrosis is the common pathological change of chronic liver diseases,and reversal of fibrosis can prevent the progression of most chronic liver diseases.The activation of hepatic stellate cells（HSCs） is considered as the central event of hepatic fibrosis,thus the traditional therapy for hepatic fibrosis was targeting to HSC and have achieved substantial efficacy in animal experiments.However,recent studies have indicated that the activation of HSCs also contributes to the hepatocyte proliferation and live regeneration.Hepatocyte nuclear factors（HNFs） consist of a group of transcription factors,which are critical for the hepatocyte differentiation and functional maintenance.Forced expression of HNFs could reduce the secretion of ECM,promote hepatocyte regeneration and improve liver function.Therefore,upregulation of HNFs presents as an ideal strategy for the treatment of hepatic fibrosis.