重组腺病毒Ad-HGF-hIL10基因治疗大鼠肝纤维化

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1.5×108 PFU的Ad-HGF、Ad-hIL10和Ad-HGF-hIL10经尾静脉注射入大鼠体内,模型组和对照组注射同剂量的0.9％氯化钠注射液.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 与模型组大鼠相比,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TBIL、ALT、AST显著低于模型组(P＜0.01),而ALB显著升高(P＜0.01),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＜0.05),白球比(0.83±0.11)与其他两个单基因治疗组Ad-HGF (0.74±0.05)和Ad-hIL-10(0.73±0.05)相比显著上升(P＜0.01).结论 用HGF和hIL-10双基因的腺病毒载体治疗大鼠肝纤维化,肝功能的改善效果明显优于单基因治疗组.

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

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.Methods Hepatic fibrosis model was established with 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 collected from rat heart,serum TBIL,ALT,AST,TP and ALB were measured.Liver biopsies were performed and microscoped.Results Compared with the model group,liver function of rats in the therapy group was obviously improved,while there is no obvious fibroplasia in the portal area.Compared with model group,the TBIL,ALT and AST level of the therapy group were obviously decreased(P<0.01) and ALB level of the therapy group was obviously increased(P<0.01).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<0.05),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).Conclusions The double-gene therapy group has better therapeutic effect than other single-gene therapy groups.