基础医学与临床 ›› 2012, Vol. 32 ›› Issue (9): 1049-1052.

• 研究论文 • 上一篇    下一篇

重组腺病毒Ad-HGF-hIL10基因治疗大鼠肝纤维化

邱红,邢继成,朱月蓉,王冰   

  1. 解放军第81医院生化科
  • 收稿日期:2011-08-24 修回日期:2011-12-02 出版日期:2012-09-05 发布日期:2012-08-28
  • 通讯作者: 邱红 E-mail:mapleqh@126.com
  • 基金资助:
    南京军区医学科技创新经费资助项目

Gene therapy for rat hepatic fibrosis with recombinant adenovirus vector carrying HGF and hIL10

  • Received:2011-08-24 Revised:2011-12-02 Online:2012-09-05 Published:2012-08-28
  • Contact: Hong QIU E-mail:mapleqh@126.com

摘要: 摘要:目的 探讨人IL-10和HGF双表达的重组腺病毒hIL10-HGF对大鼠肝纤维化的治疗效果,以期为肝纤维化的的基因治疗提供实验基础。方法 建立SD大鼠肝纤维化模型后,将1.5×108PFU的Ad-HGF、Ad-hIL10和Ad-HGF-hIL10经尾静脉注射入大鼠体内,对照组和正常组注射同剂量的生理盐水。第15天心脏采血,检测血清的肝功能指标,并取肝组织做HE染色,观察各组大鼠肝脏的病理形态。结果:与对照组大鼠相比,治疗组大鼠的肝组织损伤程度减轻,汇管区看不到明显的纤维增生。各治疗组的肝功能指标与对照组相比, TBIL、ALT、AST明显降低,ALB显著升高,肝功能得到了明显的改善,而Ad-HGF-hIL10双基因治疗组与Ad-HGF、Ad-hIL-10单基因治疗组相比,ALT、AST显著降低(P<0.01),白球比与其它两个单基因治疗组相比显著上升(P<0.01)。结论 用双基因的腺病毒载体治疗肝纤维化大鼠,肝功能的改善效果明显优于单基因治疗组。表明HGF 和hIL-10在大鼠肝纤维化的改善过程中发挥了协同作用,本实验为肝硬化的基因治疗提供了一定的实验基础。

关键词: 关键词:肝纤维化, 腺病毒, 肝细胞生长因子, 白细胞介素10, 基因治疗

Abstract: Abstract:Objective To investigate the therapeutic effect of the recombinant adenovirus vector carrying hepatocyte growth factor (HGF) and human interleukin-10 (hIL10), Ad-HGF-hIL10, on CCl4-induced hepatic fibrosis in rats and to provide experiment data for hepatic fibrosis gene therapy. Methods Hepatic fibrosis models were established by CCl4 in SD rats, and a total of 58 rats were randomly divided into 4 groups. Ad-HGF-hIL10, Ad-HGF and Ad-hIL10 were injected into the tail vein of three testing groups respectively. Control group were injected with physiological saline. On the 15th day, blood samples were obtained from the rat hearts, and the serum TBIL, ALT, AST, TP and ALB levels were measured. After the rats were sacrificed, liver biopsies were performed and the liver tissues obtained were examined by light microscope. Results Compared with the control group, liver function of rats in the therapy group was obviously improved, while there is no obvious fibroplasia in the portal area. The ALT and AST level of the Ad-HGF-hIL10 therapy group were much lower than that of the Ad-HGF and Ad-hIL10 therapy group (P<0.01), while the A/G value of the Ad-HGF-hIL10 therapy group is more higher than the Ad-HGF and Ad-hIL10 therapy groups(P <0.01). Conclusion:The double-gene therapy group has better therapeutic effect than other single-gene therapy groups. It was showed that HGF and IL-10 play a synergistic effect during hepatic fibrosis improvement. The experiment provides data for hepatic fibrosis gene therapy.

Key words: Key words:hepatic fibrosis, adenovirus, hepatocyte growth factor, interleukin-10, gene therapy