超声作用下微泡携肝细胞生长因子治疗大鼠肝纤维化的实验研究

目的 探讨超声作用下微泡携肝细胞生长因子(HGF)对大鼠肝纤维化的治疗效果。方法 构建真核表达质粒pMD18-T/HGF;将实验大鼠随机分为5组：正常组、模型组、低剂量组、中剂量组、高剂量组。建立肝纤维化模型，治疗14 d后处死大鼠，取血行检测丙氨酸转氨酶(ALT)评价肝功能，病理切片HE染色评价纤维化程度，免疫组化SABC法观察HGF蛋白，RT-PCR检测HGF mRNA。结果 治疗组治疗后血清肝功能优于模型组(P＜0.05)，低剂量组与正常组间差异有统计学意义(P＜0.05)，中、高剂量组与正常组间差异无统计学意义(P＞0.05)。病理切片示治疗组纤维化减轻;免疫组化见各治疗组HGF阳性表达，表达量随治疗剂量增高而增大(P＜0.05)。RT-PCR示各治疗组HGF mRNA表达高于模型组，且随治疗剂量的增大而增高(P＜0.05)。结论 超声作用下微泡携HGF可以有效抑制肝纤维化进程，其治疗效果在一定范围内随着治疗剂量的增大而增强。

Experimental study of ultrasound microbubble-mediated HGF gene transfer on liver fibrosis in rats

Objective To investigate the efficiency of ultrasound microbubble-mediated HGF gene transfer on liver fibrosis in rats. Methods The eukaryotic expression vector pMD18-T/HGF was constructed. The rats were randomly divided into 5 groups: normal group, model group, low dose group,middle dose group and high dose group. The rat liver fibrosis were induced. At day 14 after treatment, the rats were sacrificed, the ALT lever were evaluated, pathological evaluation of liver fibrosis were made,immunohistochemical evaluation of HGF protein expressions were observed, HGF mRNA expression were detected by RT-PCR. Results Liver 1function after the treatment showed that the treatment groups were better than model group ( P ＜ 0. 05). The difference between low dose group and normal group showed significant difference ( P ＜0.05), and the difference between middle/high dose groups and normal group showed no significant ( P ＞0. 05). Pathological results showed that the treatment groups could reduce liver fibrosis;treatment groups had the positive HGF expression by immunohistochemistry and the expression level increased with the increasement of the treatment dose ( P ＜0.05). RT-PCR showed HGF mRNA expression in the treatment groups were higher than in model group ( P ＜0.05). Conclusions Ultrasound microbubbles which carrying HGF can inhibit the process of hepatic fibrosis.