白芍总苷对免疫性肝纤维化大鼠肝组织NF-κB和TGF-β1蛋白表达的影响

目的研究免疫性肝纤维化大鼠肝组织中核转录因子-κB(nuclear factor-κB,NF-κB)和转化生长因子β1(trans-forming growth factor beta1,TGF-β1)的变化以及白芍总苷(TGP)对两者蛋白表达的影响。方法采用猪血清诱导建立大鼠肝纤维化模型,肝组织HE染色和V-G染色观察肝组织损伤及胶原表达变化;免疫组化S-P法观察NF-κB p65和TGF-β1蛋白表达;显微摄像及图像分析检测胶原、NF-κBp65和TGF-β1蛋白的表达量。结果与正常组比较,模型组大鼠肝组织明显破坏,胶原合成增加,NF-κB p65和TGF-β1表达增强(P<0.01);与模型组比较,TGP治疗组肝组织破坏减轻,纤维化程度也明显改善,胶原面积、NF-κB p65和TGF-β1表达均明显减少(P<0.01),三者呈相关性。结论NF-κB介导TGF-β1产生或活化在免疫性肝纤维化过程中可能发挥着重要作用,而TGP抑制纤维化大鼠肝组织NF-κB和TGF-β1的表达可能是TGP的抗肝纤维化主要作用机制之一。

Effects of total glucosides of paeony on protein expression of NF-kappa B and TGF-β1 in hepatic tissue of rats with immunological hepatic fibrosis

Aim To observe the protein expression of nuclear factor kappa B(NF-κB) and transforming growth factor beta-1(TGF-β1) in hepatic tissue of rats with immunological hepatic fibrosis,and evaluate the effect of total glucosides of paeony(TGP) on expression of the NF-κB p65,TGF-β1 in order to reveal the anti-hepatic fibrosis mechanism of TGP.Methods The rats were divided into four groups:normal group,model group,and TGP(120 and 240 mg·kg-1) treatment groups.Immunological hepatic fibrosis rat model was induced by injecting pig serum(ip,twice a week for 15 weeks).Rats of treatment groups were administered with TGP(ig) since the 5th week,the rats in normal and model groups were only administered with the same volume of vehicle.All rats were killed at the end of 15th week,then left livers were used to make HE and V-G staining,protein of TGF-β1 and NF-κB p65 in hepatic tissue was determined by immunohistochemical techniques,at last the collagen and protein were quantified by imaging analysis system.Results Compared with normal group,model rat hepatic tissue was destroyed,their fibrosis grades,collagen and protein expression of NF-κB p65 and TGF-β1 remarkably increased(P<0.01).Compared with model group,the above index of TGP group decreased(P<0.01).Furthermore,there were correlations among the protein expression of NF-κB p65,TGF-β1 and collagen.Conclusion NF-κB might play an important role in mediating the expression or activity of TGF-β1 in immunological liver fibrosis.TGP could inhibit protein expression of TGF-β1 and NF-κB,which was probably one of the anti-hepatic fibrosis mechanisms of TGP.