重组人肝再生增强因子对肝纤维化大鼠金属蛋白酶组织抑制因子-1基因表达的影响

Recombinant human augmenter of liver regeneration can decrease gene expression of tissue inhibitor of metalloproteinases-1 in fibrotic rats

目的 了解重组人肝再生增强因子 (hALR)对肝纤维化大鼠金属蛋白酶组织抑制因子 1(TIMP1)基因表达的影响。方法 建立CCl4中毒性及人血白蛋白免疫损伤性两种大鼠肝纤维化模型。模型完成后予不同剂量hALR(每天 5 0、10 μg/kg体重 )治疗。在不同的时间点留取大鼠肝组织标本 ,提取总RNA ,用逆转录定量聚合酶链反应 (RT PCR)测定TIMP1的基因表达水平。结果 在两种模型中低剂量hALR治疗组大鼠肝组织TIMP1的基因表达水平在治疗过程中的不同阶段与模型组差异无显著性 (P >0 .0 5 ) ;高剂量hALR组大鼠肝组织TIMP1的基因表达水平(四氯化碳模型 2 .13± 0 .2 0 ,1.3 6± 0 .13 ;白蛋白模型 3 .0 2± 0 .5 2 ,1.85± 0 .42 )均明显低于模型组(四氯化碳模型 3 .3 1± 0 .2 6,2 .40± 0 .2 3 ;白蛋白模型 4.60± 0 .73 ,3 .61± 0 .62 )。结论 重组人肝再生增强因子可抑制肝纤维化大鼠金属蛋白酶组织抑制因子 1的基因表达。

Objective To investigate the influence of recombinant human augmenter of liver regeneration (hALR) on gene expression of tissue inhibitor of metalloproteinases 1 (TIMP1) in fibrotic rats.Methods CCl 4 and albumin induced two kinds of animal models of rat experimental liver fibrosis were established and different dosages of recombinant human augmenter of liver regeneration (50?μg/kg and 10?μg/kg every day) were given.Liver specimens were obtained at different periods of treatment.Total RNA of liver tissues were isolated and TIMP1 gene expression levels were detected by reverse transcription polymerase chain reaction (RTPCR).Results In both rat models of experimental liver fibrosis,there was no significant difference in the TIMP1 gene expression level in the rat liver tissue between the low or moderate dose hALR treating group and model group in different periods of treatment.TIMP1 gene expression levels in high dose hALR treating group (CCl 4 model 2.13±0.20,1.36±0.13;albumin model 3.02±0.52,1.85±0.42 respectively) were significantly lower than those in the model group (CCl 4 model 3.31±0.26,2.40±0.23;albumin model 4.60±0.73,3.61±0.62 respectively).Conclusion Recombinant human augmenter of liver regeneration may inhibit TIMP1 gene expression in fibrotic rats.