核转录因子-κB拮抗剂PDTC抗大鼠肝纤维化作用研究

The effects of NF-κB inhibitor PDTC on rat liver fibrosis

目的:研究核转录因子κB(NF-κB)拮抗剂吡咯烷二硫代氨基甲酸铵(PDTC)抗大鼠肝纤维化的作用。方法:SD大鼠随机分为正常对照组、模型组、阴性治疗对照组和PDTC治疗组。以四氯化碳(CCl4)制备肝纤维化模型,在注射CCl4造模的同时,腹腔注射NF-κB抑制剂PDTC。注射6周末处死大鼠,取肝组织,分别用免疫组化法及RT-PCR法检测NF-κB、TNF-α、Ⅰ、Ⅲ型胶原在4个组中的表达。结果:(1)免疫组化法检测结果:NF-κB主要分布在肝细胞核内,TNF-α位于肝细胞的胞浆,Ⅰ、Ⅲ型胶原位于汇管区和中央静脉周围。4种蛋白表达正常对照组为-或+,模型组和阴性治疗对照组均为强阳性表达(+++),PDTC治疗组多为+,少数++表达,PDTC治疗组与模型组间比较,差异均有统计学意义(P<0.05)。(2)RT-PCR检测结果:4种蛋白表达量正常对照组最低,肝纤维化模型组及阴性治疗对照组表达量均明显升高,两组比较差异无统计学意义(P>0.05)。PDTC治疗组表达量较模型组明显下降,两组比较差异均有统计学意义(P<0.01)。结论:NF-κB拮抗剂PDTC能明显抑制细胞外基质的合成,具有明显的抗肝纤维化作用。

Objective： To study the effects of NF-κB inhibitor pyrrolidine dithiocarbamate（PDTC） on rat liver fibrosis.Methods： SD rats were randomly divided into normal control group,model group,negative control group and PDTC treatment group.The rats in model group were injected with CCl4 alone.The rats in PDTC group were intraperitoneally injected with CCl4 and PDTC simultaneously and the rats in normal solu tion group were injected with same volume of normal solution instead of PDTC.Six weeks later,the rats were sacrificed and NF-κB,TNF-α and collagen typesⅠand Ⅲ in liver tissues were detected by immunohistochemistry and reverse transcription polymerase chain reaction（RT-PCR）.Results：（1） Immunohistochemistry： NF-κB and TNF-α expression mainly in nuclei and cytoplasm respectively,collagen typesⅠand Ⅲ expression chiefly around the portal area and central vein.4 kinds of proteins expression for the or ＋ in normal control group,for ＋＋＋ in model group and negative control group,for chiefly ＋ and a few ＋＋ in PDTC treatment group,and the difference had statistical significance between PDTC treatment group and model group（P0.05）.（2） RT-PCR： The expressions of 4 kinds of proteins were the lowest in normal control group and were the highest in model group and negative control group.There was no significant difference between model group and negative control group（P〈0.05）.The expressions of 4 kinds of proteins were lower in PDTC treatment group than that in model group and the difference had statistical significance（P0.01）.Conclusion： PDTC decreases the deposition of collagen typesⅠand Ⅲ,and attenuates the development of liver fibrosis.