NF-κB、TGF-β1在肝纤维化中的改变及护肝片的影响

摘要/Abstract

摘要： 目的探讨中、晚期纤维化大鼠肝组织核转录因子-κB(NF-κB)、转化生长因子β₁(TGF-β₁)的变化及护肝片对其影响。方法采用12.5%CCl₄诱导的大鼠肝纤维化模型,自造模之日起,大鼠分组灌胃给药(护肝片921 mg·kg^-1)或溶媒,每日1次,直至8或13周末,分别处死动物,取左叶肝组织石蜡包埋,制作组织芯片,免疫组化S-P法检测大鼠肝组织NF-κB p65、TGF-β₁蛋白的表达,并用MetaMorph图像分析系统对NF-κB p65、TGF-β₁蛋白表达量进行定量分析。结果(1)模型复制8和13周,模型组的肝损伤及其纤维化分级均明显高于正常组(P＜0.01),护肝片组的肝损伤及其纤维化分级均轻于模型组。(2)模型复制8和13周,模型组NF-κB p65、TGF-β₁蛋白的表达较正常组明显增强(P＜0.01)；NF-κB p65蛋白和TGF-β₁蛋白的表达之间呈显著的正相关(P＜0.01);(3)护肝片显著抑制8、13周纤维化肝组织NF-κB p65、TGF-β₁蛋白的表达(P＜0.01)。结论护肝片可减轻肝组织的损伤及其纤维化程度,抑制NF-κB、TGF-β₁的表达可能是其抗肝纤维化作用的靶点之一。

关键词: 肝硬化/病理学, 护肝片, 抗结核药, 肝纤维化

Abstract: Objective To study the dynamic changes in the expression of nuclear factor kappa B(NF-κB)and transforming growth factor beta-1(TGF-β₁)in the development of middle and late stage of rat hepatic fibrosis,and the effect of liver-aid tablets on them.Methods SD rats were divided into three groups:normal control,model control and group of liver-aid tablets.CCl₄(12.5%,4ml·kg^-1)was injected sub-cutaneously in model rat twice a week for 8 and 13 weeks.The drug(921mg·kg^-1 in the group of liver-aid tablets,but 0.5% CMC-Na in control groups)was taken orally once a day for 8 and 13 weeks.The rats were killed at the end of 8th and 13th week,respectively.The left liver tissue was then used to make tissue microarrays(TMA).The TMA sections were used for Immunohistochemistry(IHC)to detect the protein expression of NF-κB p65 and TGF-β₁.The NF-κB p65 and TGF-β₁ Results of IHC were quantified by MetaMorph imaging analysis system.Results (1)During 8 and 13 weeks,the degrees of liver injury and fibrosis grades in the model group were higher than those in the normal group(P＜0.01),which was amelionated remarkably by liver-aid tablets treatment.(2)The protein expression of NF-κB p65 and TGF-β₁ in the model group was stronger than that in the normal group during 8 and 13 weeks(P＜0.01),the protein expression of NF-κB p65 and TGF-β₁ were correlated to each other during 8 and 13 weeks(P＜0.01).(3)Liver-aid tablets inhibited the protein expression of NF-κB p65 and TGF-β₁ of fibrotic liver tissue in rats during 8 and 13 weeks(P＜0.01).Conclusion Liver-aid tablets have anti-fibrosis effects on CCl₄-induced rat liver fibrosis,which might be performed through the pathway of inhibiting the expression of NF-κB and TGF-β₁.

Key words: Hepatic fibrosis/Pathology, Liver-aid tablets, Aantituberculous medicines, Liver fibrosis

吴义春,吴强,杨雁,杨枫,陈敏珠,. NF-κB、TGF-β₁在肝纤维化中的改变及护肝片的影响[J]. 中国防痨杂志, 2007, 29(4): 317-320.

Wu Yichun¹,Wu Qiang,Yang Yan,et al. Change of NF-kappa B,transforming growth factor beta-1 in the development of rat hepatic fibrosis and the effect of Liver-aid Tablets on them[J]. Chinese Journal of Antituberculosis, 2007, 29(4): 317-320.

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NF-κB、TGF-β₁在肝纤维化中的改变及护肝片的影响

Change of NF-kappa B,transforming growth factor beta-1 in the development of rat hepatic fibrosis and the effect of Liver-aid Tablets on them

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