反义核酸技术在受胶原基因表达调控的肝纤维化研究中的应用

肝纤维化是慢性肝损伤的修复反应，以胶原为主的细胞外基质（ECM）在肝内大量沉积的病理过程。其形成机制较为复杂，各种细胞因子彼此相互作用，形成细胞因子网络，共同调控肝纤维化的发生、发展。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。反义核酸技术是一种发展迅速并极富应用前景的基因控制技术。它是利用DNA或RNA分子通过Watson Crick碱基配对原则与目的基因的mRNA互补结合，通过各种机制使其降解或抑制其编码蛋白的翻译，从而抑制目的基因的表达，主要包括反义寡核苷酸技术、RNA干扰技术和三股螺旋结构寡核苷酸技术。本文综述了应用反义核酸技术调控相关基因的表达来防治肝纤维化的研究现状。

Progress of antisense nucleic acids techniques in gene therapy for the treatment of collagen gene expression in liver fibrosis

Liver fibrosis is defined as a wound-healing response to a variety of chronic stimuli, and is characterized by an excessive deposition of extracellular matrix (ECM) which mainly consists of collagen proteins. The mechanism of hepatic fibrosis is complicated. A big number of cytokines play important roles in the pathogenesis of hepatic fibrosis. 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. Antisense nucleic acids techniques have been shown to represent a powerful method for manipulating gene expression in organisms and are developed into a promising therapeutic too. Antisense molecules bind to DNA or RNA through classic Watson and Crick base paring and can be used to alter protein function or inhibit expression. Several techniques of action have been demonstrated, including antisense oligonucleotide (ASON), small-interfering RNAs (siRNAs) and triplehehx forming oligonucleotide (TFO). This paper reviews the researches progress in gene therapy for the treatment of gene expression in liver fibrosis.