CAJ | 학술논문

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。
목적：관찰필격렬동대체외배양적유혹무반괴특이성항원양화저밀도지단백（ oxLDL）자격적뇨독증ApoE－／－소서조절성화효응T세포（ Treg／Teff）수평화공능상관인자적영향급가능궤제。방법：통과량보외과수술법건립뇨독증 ApoE－／－소서적동물모형，이불동농도필격렬동（2μmol／L 화20μmol／L ）급 PPARγ길항제GW9662（5μmol／L）대유혹무oxLDL（2 mg／L）자격적뇨독증모형서비세포작용12 h후，류식세포술검측CD4＋CD25＋Foxp3＋Treg급IFN-γ＋CD4＋Teff세포수평，실시형광정량PCR검측Foxp3급IFNγ적mRNA표체。결과：oxLDL체외유도뇨독증ApoE－／－소서비세포Treg／Teff실형。필격렬동상조oxLDL억제하적Treg급Foxp3적표체，차작용불능피GW9662길항；하조유혹무oxLDL자격하Teff급IFNγ적표체，차작용가피GW9662길항。결론：ox-LDL체외유도뇨독증모형서Treg／Teff실형，필격렬동통과PPARγ비의뢰／의뢰궤제조정Treg／Teff실형。
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.