Reduction of fibrosis in a rat model of non-alcoholic steatohepatitis cirrhosis by human HGF gene transfection using electroporation
Reduction of fibrosis in a rat model of non-alcoholic steatohepatitis cirrhosis by human HGF gene transfection using electroporation
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DOI：
10.1111/j.1440-1746.2007.05111.x
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发表时间：
2008-08-01
影响因子：
4.1
通讯作者：
Takemura, Hirofumi
中科院分区：
文献类型：
--
作者：
Kiyama, Shigeru;Yamada, Takuya;Takemura, Hirofumi
背景和目的：为研究电穿孔法（electroporation，EP）转染肝细胞生长因子（hepatocyte growth factor，HGF）基因对非酒精性脂肪性肝炎（non-alcoholic steatohepatitis，NASH）大鼠肝脏组织学的影响，采用5周龄雄性Wister大鼠，给予胆碱缺乏饲料12周，制备NASH大鼠肝脏模型。使用三组大鼠：G（+）组使用EP转染GFP基因，H（+）组使用EP转染HGF基因，H（-）组仅注射HGF基因。结果：NASH肝组织中Azan阳性率（APR）和Sudan阳性率（SPR）均明显高于正常肝组织。G（+）组和H（-）组的APR没有降低，但H（+）组的非电穿孔区和电穿孔区的APR显著降低。对于SPR，G（+），H（-）和H（+）groups.Conclusion之间没有显着差异：肝纤维化的改善是不显着时，直接注射的HGF基因单独使用，但它是由EP的同时使用增强。然而，在脂肪组分中未观察到有效性。这些结果表明，通过EP转染HGF基因可能导致不可逆性脂肪肝的改善。
Background and Aim: To study the histological changes caused by transfection of the hepatocyte growth factor (HGF) gene using electroporation (EP) in a non-alcoholic steatohepatitis (NASH) cirrhotic liver model.Methods: NASH cirrhotic livers were prepared by administering a choline-deficient diet to 5-week-old male Wister rats for 12 weeks. Three groups of rats were used: rats in the G(+) group were transfected with the GFP gene using EP, rats in the H(+) group were transfected with the HGF gene using EP, and rats in the H(-) group were only injected with the HGF gene. Rats were sacrificed 2 days after gene transfection, and the Azan positive rate (APR) and Sudan positive rate (SPR) were calculated to evaluate fibrosis and fatty changes.Results: The APR of the NASH cirrhotic livers was significantly higher than that in the normal livers. The APR did not decrease in the G(+) group and the H(-) group, but decreased significantly in the nonelectroporated as well as electroporated areas of the H(+) group. For SPR, there were no significant differences between the G(+), H(-), and H(+) groups.Conclusion: The improvement of fibrosis was not significant when a direct injection of the HGF gene was used alone, but it was enhanced by the concomitant use of EP. However, no efficacy was observed in fat components. These findings suggest that transfection of the HGF gene by EP may lead to an improvement of irreversible cirrhotic livers to reversible fatty livers.