吡格列酮对尿毒症 ApoE－／－小鼠调节性和效应T 细胞平衡的影响  

Effect of pioglitazone on balance of regulatory and effector T cells of uremic apolipoprotein E knockout mice in vitro

作　　者：申燕[1] 肖嫣[2] 王丽君[3] 赵艳[2] 田雨灵[2] 梁潇[2] 尹爱萍[1] 

机构地区：[1]西安交通大学医学院第一附属医院肾病中心肾内科,陕西西安710061 [2]西安交通大学医学院第一附属医院心内科,陕西西安710061 [3]西安交通大学医学院第一附属医院西安交通大学环境与疾病相关基因教育部重点实验室,陕西西安710061

出　　处：《中国病理生理杂志》2015年第5期802-807,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81200541);中央高校基本科研业务费专项资金(No.xjj2012065)

摘　　要：目的:观察吡格列酮对体外培养的有或无斑块特异性抗原氧化低密度脂蛋白(ox LDL)刺激的尿毒症Apo E-/-小鼠调节性和效应T细胞(Treg/Teff)水平和功能相关因子的影响及可能机制。方法:通过两步外科手术法建立尿毒症Apo E-/-小鼠的动物模型,以不同浓度吡格列酮(2μmol/L和20μmol/L)及PPARγ拮抗剂GW9662(5μmol/L)对有或无ox LDL(2 mg/L)刺激的尿毒症模型鼠脾细胞作用12 h后,流式细胞术检测CD4+CD25+Foxp3+Treg及IFN-γ+CD4+Teff细胞水平,实时荧光定量PCR检测Foxp3及IFNγ的mRNA表达。结果:ox LDL体外诱导尿毒症Apo E-/-小鼠脾细胞Treg/Teff失衡。吡格列酮上调ox LDL抑制下的Treg及Foxp3的表达,此作用不能被GW9662拮抗;下调有或无ox LDL刺激下Teff及IFNγ的表达,此作用可被GW9662拮抗。结论:oxLDL体外诱导尿毒症模型鼠Treg/Teff失衡,吡格列酮通过PPARγ非依赖/依赖机制调整Treg/Teff失衡。AIM：To investigate the effects of pioglitazone on the quantity and function-related factors of regu-latory and effector T cells （ Treg and Teff ） of uremic apolipoprotein E knockout mice in vitro with or without the stimulation of atherosclerotic plaque-specific antigen oxidized low-density lipoprotein （ oxLDL） .METHODS：Uremic apolipoprotein E knockout mouse model was established by 2-step surgical procedure.After intervention with different concentrations （ 2μmol/L and 20μmol/L） of pioglitazone and PPARγantagonist GW9662 （5μmol/L） on splenocytes of uremic mice for 12 h in the presence or absence of oxLDL （2 mg/L）, the levels of CD4 ＋CD25 ＋Foxp3 ＋Treg and IFNγ＋CD4 ＋Teff were de-termined by flow cytometry.The mRNA expressions of Foxp3 and IFNγwas detected by real-time fluorescent quantitative PCR.RESULTS：In vitro, oxLDL induced a Treg/Teff imbalance in splenocytes from the uremic mice.Pioglitazone up-regulated the level of Treg and mRNA expression of Foxp3 in the presence of oxLDL, which was not antagonized by GW9662.Meanwhile, pioglitazone downregulated the level of Teff and mRNA expression of IFNγin the presence or ab-sence of oxLDL, which was reversed by GW9662.CONCLUSION：oxLDL induces a Treg/Teff imbalance in uremic apo-lipoprotein E knockout mice.Pioglitazone modulates the Treg/Teff imbalance probably through PPARγ-independent and-dependent mechanisms.

关 键 词：吡格列酮 过氧化物酶体增殖物激活受体Γ 尿毒症 调节性T细胞 效应T细胞 

分 类 号：R363[医药卫生—病理学] R692[医药卫生—基础医学]