吡格列酮对尿毒症apoE^(-/-)小鼠调节性T细胞和动脉粥样硬化的影响  

Effects of pioglitazone on Treg cells and atherosclerosis in uremic apoE^(-/-)mice

作　　者：申燕[1] 袁祖贻[2] 肖嫣 吴岳[2] 赵燕[2] 田雨灵[2] 刘卫民[2] 王丽君[2] 梁萧[2] 陈涛[2] 耿涛[4] 

机构地区：[1]西安交通大学医学院第一附属医院肾内科,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]北京市西山医院心内科,北京100144 [4]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》2010年第5期833-838,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30871043;No.30971219);陕西省卫生厅基金资助项目(No.08D26)

摘　　要：目的:观察吡格列酮(Pio)对尿毒症apoE基因敲除(apoE-/-)小鼠调节性T细胞(Treg)和动脉粥样硬化(atherosclerosis,AS)的影响。方法:ApoE-/-小鼠通过二步外科手术法建立尿毒症模型,对照组行假手术。造模后检测肾功能判断造模是否成功。实验动物分为:尿毒症Pio干预组(UP)、尿毒症安慰剂组(UO)及对照安慰剂组(CO),分别以Pio或安慰剂干预8周。干预结束后检测肾功能、血脂及血糖;血清转化生长因子β1(TGF-β1)及干扰素γ(IFN-γ)浓度;脾脏Treg比率;主动脉叉状头/翅膀状螺旋转录因子(Foxp3)、细胞毒性T淋巴细胞抗原-4(CTLA-4)及IFN-γmRNA的表达;主动脉根部AS斑块相对面积。结果:手术后肾功能检测提示造模成功。干预结束后UO组与CO组相比,主动脉根部斑块相对面积显著增大;脾脏Treg比率下降;血清TGF-β1浓度降低、IFN-γ浓度升高;主动脉Foxp3及CTLA-4mRNA表达下调、IFN-γmRNA表达上调。Pio干预能逆转上述指标的改变,即UP组与UO组相比,主动脉根部斑块面积显著缩小;脾脏Treg比率上升;血清TGF-β1浓度升高、IFN-γ浓度降低;主动脉Foxp3及CTLA-4mRNA表达上调、IFN-γmRNA表达下调。结论:Pio可上调尿毒症apoE-/-鼠体内受损Treg的数量和功能,校正Treg/效应性T细胞(effectorTcell,Teff)失衡和延缓其主动脉加速发展的AS,而此作用与改善糖脂代谢无关。AIM：To observe the effects of PPAR-γ agonist pioglitazone （Pio） on regulatory T cells （Treg） and atherosclerosis （AS） in apolipoprotein E knockout （apoE-/-） mice. METHODS：Uremic apoE-/-mice were created by a twostep surgical procedure. Control apoE-/-mice were shamoperated. The renal functions were detected 2 weeks after inducing uremia to evaluate the efficiency of the model. Three subgroups of experimental mice were set up：uremia Pio intervention group （UP）,uremia placebo group （UO） and control placebo group （CO）,which were treated with Pio （20 mg·kg-1.d-1） or placebo for 8 weeks,respectively. After the intervention was finished,the renal functions,serum lipid profile and glucose,serum concentrations of transforming growth factor β1 （TGF-β1 ） and interferon gamma （IFN-γ）,Treg ratio in spleen,the expression of forkhead/winged helix transcription factor （Foxp3）,cytotoxicity T lymphocyte antigen-4 （CTLA-4） and IFN-γ mRNA in aorta,AS lesion relative area in aortic root were determined. RESULTS：The renal functions after operation indicated that the uremic model was successful. Compared to CO group,the aortic root plaque relative area increased significantly,Treg ratio in spleen and serum concentration of TGF-β1 decreased,IFN-γ increased,mRNA expression of Foxp3 and CTLA-4 decreased,IFN-γ increased in UO group. Compared to UO group,Pio intervention reversed the above changes：aortic root plaque relative area decreased significantly,Treg ratio in spleen and serum concentration of TGF-β1 increased,IFN-γ decreased,mRNA expression of Foxp3 and CTLA-4 increased,IFN-γ decreased in UP group. CONCLUSION：Pio upregulates the Treg in quantity and function,corrects the imbalance of Treg/effector T cells （Teff） and ameliorates aortic accelerated AS in uremic apoE-/-mice. However,these effects are independent of hypoglycemia and hypolipemia.

关 键 词：尿毒症 ApoE-/-鼠 动脉粥样硬化 调节性T细胞 吡格列酮 

分 类 号：R692[医药卫生—泌尿科学]