腺相关病毒介导的血红素加氧酶-1基因转移抑制大鼠微结节性肝硬化的进展。
Adeno-associated virus-mediated heme oxygenase-1 gene transfer suppresses the progression of micronodular cirrhosis in rats.
作者信息
Tsui Tung-Yu, Lau Chi-Keung, Ma Jian, Glockzin Gabriel, Obed Aiman, Schlitt Hans-J, Fan Sheung-Tat
机构信息
Department of Surgery, Center for the Study of Liver Disease, the University of Hong Kong, Pokfulam, Hong Kong.
出版信息
World J Gastroenterol. 2006 Apr 7;12(13):2016-23. doi: 10.3748/wjg.v12.i13.2016.
AIM
To test the hypothesis that enhancement of the activity of heme oxygenase can interfere with processes of fibrogenesis associated with recurrent liver injury, we investigated the therapeutic potential of over-expression of heme oxygense-1 in a CCl(4)-induced micronodular cirrhosis model.
METHODS
Recombinant adeno-associated viruses carrying rat HO-1 or GFP gene were generated. 1x 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.
CONCLUSION
Enhancement of HO activity in the livers suppresses the development of cirrhosis.
目的
为了验证增强血红素加氧酶活性可干扰与复发性肝损伤相关的纤维化形成过程这一假说，我们在四氯化碳诱导的小结节性肝硬化模型中研究了过表达血红素加氧酶-1的治疗潜力。
方法
构建携带大鼠HO-1或GFP基因的重组腺相关病毒。在诱导肝纤维化时通过门静脉注射给予1×10¹²vg腺相关病毒。
结果
用rAAV/HO-1使HO-1过表达预处理大鼠肝脏，可稳定地显著提高HO酶活性。与对照组相比，rAAV/HO-1转导的动物小结节性肝硬化的发展受到显著抑制。与对照组相比，rAAV/HO-1转导的动物门静脉高压明显减轻，而收缩压无显著变化。这一发现伴随着rAAV/HO-1转导肝脏中肝脏生化指标的改善、浸润巨噬细胞减少和肝星状细胞（HSC）活化减少。
结论
肝脏中HO活性的增强可抑制肝硬化的发展。
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