罗格列酮对日本血吸虫病肝纤维化小鼠肝组织核因子-κB和过氧化物酶体增殖物激活受体γ表达的影响  

Effect of rosiglitazone on the activity of hepatic nuclear factor-kappa B and expression of peroxisome proliferator-activated receptor-γ in mice with liver fibrosis due to schistosoma japonicum infection

作　　者：谌辉[1] 张景辉[2] 刘文琪[3] 贺永文[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院传染科,湖北省武汉市430030 [2]华中科技大学同济医学院附属协和医院外科实验室,湖北省武汉市430030 [3]华中科技大学同济医学院寄生虫学教研室,湖北省武汉市430022

出　　处：《世界华人消化杂志》2007年第7期741-745,共5页World Chinese Journal of Digestology

基　　金：湖北省自然科学基金资助项目;No.2005ABA170~~

摘　　要：目的:观察日本血吸虫病肝纤维化小鼠肝脏肝组织核因子-κB(NF-κB)的活性和过氧化物酶体增殖物激活受体γ(PPARγ)的表达,及PPARγ配体罗格列酮对其表达的影响.方法:50只昆明小鼠,随机分为正常对照组、感染对照组、吡喹酮治疗组、罗格列酮治疗组及罗格列酮加吡喹酮治疗组.除正常对照组外,其余各组均建立血吸虫病肝纤维化小鼠模型.用HE染色观察肝组织光镜下的病理改变.用Western blot方法,实时荧光定量PCR反应观察小鼠肝组织NF-κB的活性变化与PPARγmRNA的表达.结果:罗格列酮加吡喹酮治疗组小鼠肝脏的炎性反应和纤维化病理改变较其他模型组轻(P<0.05).感染对照组NF-κB活性(141.11±15.37)最强,明显高于其余各组(正常对照组:78.89±18.12;吡喹酮组:112.89±20.17;罗格列酮组:108.89±20.47;罗格列酮加吡喹酮组:88.89±19.34)(P<0.05).感染对照组[-27.315±(-6.348)]及吡喹酮治疗组[-25.647±(-5.694)]PPARγmRNA表达较正常对照组[-16.557±(-3.022)]及罗格列酮治疗组[-18.217±(-4.498)]、罗格列酮加吡喹酮治疗组[-18.212±(-3.909)]显著减弱(P<0.05).结论:PPARγ及NF-κB在血吸虫病肝纤维化形成中起一定作用.PPARγ配体罗格列酮有明显的抗日本血吸虫病肝纤维化效应,其抗纤维化机制与PPARγ配体激活PPARγ表达的同时抑制NF-κB的活性有关.AIM： To investigate the effect of rosiglitazone on the binding activity of hepatic nuclear factor-kappa B （NF-κB） and the expression of peroxisome proliferator-activated receptor gamma （PPARγ） in mice with liver fibrosis caused by schistosoma japonicum infection. METHODS： A total of 50 mice were randomly and averagely divided into group A, B, C, D and E. The mice in group A served as normal controis, while those in the other four groups were infected with schistosoma japonicum to induce the model of liver fibrosis. Besides, the mice in group C, D and E were treated with praziquantel, rosiglitazone, and praziquantel plus rosiglitazone, respectively. HE staining was used to observe the pathological changes of liver tissues under light microscope, and Western blot and real-time fluorescent quantitative polymerase chain reaction （RFQ-PCR） were performed to detect the activity of NF-κB and mRNA expression of PPARy. RESULTS： The inflammatory and fibrotic degrees were obviously alleviated in group E, which were the lightest among those groups with schistosomiasis （P 〈 0.05）. The activity of NF-κB was the highest in group B （141.11 ± 15.37）, significantly higher than that in group A, C, D and E （78.89 ± 18.12, 112.89 ± 20.17, 108.89 ± 20.47, 88.89 ±19.34）（P 〈 0.05）. The level of PPARy mRNA was markedly higher in group A [-16.557±（-3.022）], D [-18.217±（4.498）] and E [-18.219±（-3.909）] than that in group B [-27.315±（-6.348）] and C [-25.647± （-5.694）] （P 〈 0.05）. CONCLUSION： NF-κB and PPARy may be involved in the pathogenesis of liver fibrosis due to schistosoma japonicum infection. Rosiglitazone, a ligand of PPARγ, is obviously effective in the treatment of this disease by up-regulating PPARy expression and reducing NF-κB activity.

关 键 词：罗格列酮 日本血吸虫病 核因子-ΚB 过氧化物酶体增殖物激活受体Γ 

分 类 号：R532.21[医药卫生—内科学] R575.2[医药卫生—临床医学]