罗格列酮对四氯化碳诱导大鼠早期肝纤维化的抑制作用

Inhibitory Effects of Rosiglitazone on Carbon Tetrachloride-induced Early Liver Fibrogenesis in Rats

目的探讨过氧化酶增殖物激活受体γ(PPARγ)激动剂罗格列酮(rosiglitazone)对四氯化碳(CCl4)诱导大鼠早期肝纤维化的抑制作用。方法建立四氯化碳诱导大鼠早期肝纤维化模型,同时给予罗格列酮(1mg/kg)治疗,造模结束后分别检测正常对照组、四氯化碳模型组、罗格列酮干预组大鼠血清中Ⅲ型前胶原肽(PⅢP)、Ⅳ型胶原、透明质酸(HA)、层黏连蛋白(LN)、肿瘤坏死因子α(TNF-α)的浓度,并做肝病理组织学检查;用RT-PCR方法检测Ⅰ型前胶原mRNA的表达。结果同四氯化碳模型组相比,罗格列酮干预组肝组织中Ⅰ型胶原mRNA表达明显降低(P<0.01),血清中PⅢP、Ⅳ型胶原、LN、HA、TNF-α浓度显著降低(均P<0.05),病理组织学检查显示肝纤维化程度亦显著减轻。结论PPARγ受体激动剂罗格列酮通过抑制胶原基因表达从而在大鼠体内发挥早期抗纤维化的作用。

Objective To investigate the effect of rosiglitazone, a peroxisome proliferator-αctivated receptor γ （PPAR-γ） ligand, on carbon tetrachloride induced early liver fibrogenesis in rats. Methods Early liver fibrogencsis in the rats was induced by carbon tetraehloride and treated with rosiglitazone （ 1 mg/kg body weight） simultaneously. The serum contents of PⅢP. type Ⅳ collagen, HA, LN and TNF-α were determined in normal control group, model group, rosiglitazonc-treated group respectively. Pathological examination of the liver was done. RT-PCR was performed to detect the expression of procollagen type Ⅰ mRNA. Results As compared with model group, the expression of procollagen type Ⅰ mRNA in rosiglitazone treated group was significantly decreased （P〈0.01）. and the serum levels of PⅢ P. type Ⅳ collagen, l,N. HA and TNF-α were also decreased （P 〈0.05）. The pathological examination showed the liver fibrogenesis in rosiglitazone-treated group was obviously milder than in model group. Conclusion Rosiglitazone had the anti-fibrotic effect on the early liver fibrosis in rats by inhibiting the expression of collagen gene.