目的研究ApoE~(-/-)小鼠体内吡格列酮(PIO)是否通过TGF-β信号通路和T细胞调节性免疫机制来发挥抗动脉粥样硬化的作用。方法动脉粥样硬化ApoE~(-/-)小鼠模型连续8周每日灌胃给予PIO(日剂量20 mg/kg)。免疫组化对动脉病变组织中TGF-β信号通路相关因子、IFN-γ~+细胞及Foxp3~+细胞的表达水平进行检测。体外研究中,用特异性抗原氧化低密度脂蛋白(ox LDL)刺激原代培养的ApoE~(-/-)小鼠脾脏细胞,并与PIO或PIO~+PPARγ阻断剂GW9662共同孵育。流式细胞术检测CD4~+IFN-γ~+细胞和CD4~+CD25~+Foxp3~+细胞的水平。结果PIO可通过提高TGFβ1(P<0.01),TGFβRI(IP<0.05)和p-Smad3(P<0.05)的表达量、抑制Smad7(P<0.05)的表达量来缓解ApoE~(-/-)小鼠动脉粥样硬化的病变程度。体外实验表明,PIO处理后原代小鼠脾细胞中IFN-γ的m RNA水平显著下调(P<0.05),而Foxp3的m RNA水平显著上调(P<0.05)。流式细胞术表明PIO处理后CD4~+IFN-γ~+细胞(P<0.05)和CD4~+CD25~+Foxp3~+细胞(P<0.05)的表达量明显上升,而PPARγ阻断剂GW9662可阻断PIO对两种细胞的调控作用。结论PIO可能通过调控TGF-β/Smad信号通路及PPARγ介导的Th1/Treg细胞水平抑制ApoE~(-/-)小鼠的动脉粥样硬化病变。 Objective To investigate whether pioglitazone (PIO) exerts its anti-atherosclerosis effect in TGF-β signaling pathway and T cell regulatory immune system in ApoE ~ (- / -) mice. Methods ApoE ~ (- / -) mouse model of Atherosclerosis was administered intragastrically with PIO (daily dose 20 mg / kg) for 8 weeks. Immunohistochemical detection of TGF-β signaling pathway related factors, IFN-γ ~ + cells and Foxp3 ~ + cells in arterial lesions. In vitro studies, primary cultured ApoE ~ (- / -) mice spleen cells were stimulated with oxLDL and incubated with PIO or PIO ~ + PPARγ antagonist GW9662. The levels of CD4 ~ + IFN-γ ~ + cells and CD4 ~ + CD25 ~ + Foxp3 ~ + cells were detected by flow cytometry. Results PIO could relieve ApoE (- / -) expression by increasing the expression of TGFβ1 (P <0.01), TGFβRI (P <0.05) and p-Smad3 The degree of atherosclerosis in mice. In vitro experiments showed that the m RNA level of IFN-γ in splenocytes of PIO-treated mice was significantly decreased (P <0.05), while that of Foxp3 was significantly increased (P <0.05). Flow cytometry showed that the expression of CD4 ~ + IFN-γ ~ + cells (P <0.05) and CD4 ~ + CD25 ~ + Foxp3 ~ + cells (P <0.05) increased significantly after PIO treatment, while PPARγ blocker GW9662 Can block the regulation of PIO on both cells. Conclusion PIO may inhibit the atherosclerosis in ApoE ~ (- / -) mice by regulating the TGF-β / Smad signaling pathway and PPARγ-mediated Th1 / Treg cell level.