肝纤维化基因治疗的进展

Progress in Gene Therapy of Liver Cirrhosis

肝硬化是慢性肝病晚期的组织学改变 ,以纤维组织大量增生和肝小叶结构无序化为特征 ,因此又称肝纤维化。近年来随着分子生物学的发展 ,肝纤维化的分子机制逐渐得以阐明 ,从而使肝纤维化的基因治疗成为可能。肝纤维化的基因治疗主要起到阻止纤维化发展、刺激肝细胞分裂和肝组织结构重建三方面的作用。目前 ,常用的方法一般是通过缺陷病毒 (如腺病毒 )转入特定的细胞因子和酶 (如肝细胞生长因子、转化生长因子β1受体、基质金属蛋白酶等 )的基因 ,通过靶细胞表达这些因子作用于受损的肝脏 。

Liver cirrhosis is a common progressive pathological lesion in the late stage of chronic liver disease, which is characterized by disorganization of normal hepatic structure of regenerative nodules and hyperplasia of fibrotic tissues. In recent years, with the development of molecular biology, the molecular mechanisms underlying liver cirrhosis has been revealed more and more, which makes the therapy at the gene level possible. The ideal strategy for the treatment of liver cirrhosis should include prevention of fibrogenesis, stimulation of hepatocyte proliferation and reorganization of the liver architecture. Several gene therapy approaches for treatment of liver cirrhosis have been developed by transfer of some genes of cytokines and enzymes ( e.g HGF,TGFβ 1R,MMPs ). These gene therapies can inhibit fibrogenesis and hepatocyte apoptosis and also produce resolution of fibrosis in the cirrhotic liver. Thus, gene therapy may be potentially useful for the treatment of liver cirrhosis, which is otherwise fatal and untreatable by conventional therapy.