Adeno-associated virus-mediated heme oxygenase-1 gene transfer suppresses the progression of micronodular cirrhosis in rats
Adeno-associated virus-mediated heme oxygenase-1 gene transfer suppresses the progression of micronodular cirrhosis in rats作者机构:Centre for the Study of Liver Disease and Department of Surgery the University of Hong Kong Pokfulam Hong Kong Department of Surgery University of Regensburg Medical Centre Regensburg Germany
出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))
年 卷 期:2006年第12卷第13期
页 面:2016-2023页
核心收录:
学科分类:1002[医学-临床医学] 100201[医学-内科学(含:心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
主 题:Cirrhosis Portal hypertension Heme oxygenase Gene therapy Adeno-associated virus
摘 要:AIM: To test the hypothesis that enhancement of the activity of heine oxygenase can interfere with processes of fibrogenesis associated with recurrent liver injury, we investigated the therapeutic potential of over-expression of heine oxygense-1 in a CCl4-induced micronodular cirrhosis model. METHODS: Recombinant adeno-associated viruses carrying rat HO-1 or GFP gene were generated, 1×10^12 vg of adeno-associated viruses were administered through portal injection at the time of the induction of liver fibrosis. RESULTS: Conditioning the rat liver with over-expression of HO-1 by rAAV/HO-1 significantly increased the HO enzymatic activities in a stable manner. The development of micronodular cirrhosis was significantly inhibited in rAAV/HO-1-transduced animals as compared to controls. Portal hypertension was markedly diminished in rAAV/HO-1-transduced animals as compared to controls, whereas there are no significant changes in systolic blood pressure. This finding was accompanied with improved liver biochemistry, less infiltrating macrophages and less activated hepatic stellate cells (HSCs) in rAAV/ HO-1-transduced livers. CONCLUSIONS: Enhancement of HO activity in the livers suppresses the development of cirrhosis.