首页> 中文期刊> 《中国病理生理杂志》 >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

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

         

摘要

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.%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( oxLDL)刺激的尿毒症ApoE-/-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 ApoE-/-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oxLDL(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:oxLDL体外诱导尿毒症ApoE-/-小鼠脾细胞Treg/Teff失衡。吡格列酮上调oxLDL抑制下的Treg及Foxp3的表达,此作用不能被GW9662拮抗;下调有或无oxLDL刺激下Teff及IFNγ的表达,此作用可被GW9662拮抗。结论:ox-LDL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。

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