【摘要】 目的探讨吡格列酮预防非肥胖糖尿病(NOD)小鼠胰岛炎的机制及过氧化物酶体增殖活化受体γ(PPARγ)的作用。方法 (1)4周龄NOD雌鼠随机分为吡格列酮组及对照组,分别摄食含0.02%吡格列酮的混合饲料和普通营养饲料。(2)各组取12周龄未发病NOD鼠胰腺组织HE染色观察胰岛炎情况;RT-PCR半定量检测脾脏IL-4、IFN-γ和核因子PPARγmRNA表达水平;ELISA法测定脾脏核因子PPARγ活性。结果 (1)12周龄时胰岛炎积分吡格列酮组低于对照组(1.79±0.75VS 2.38±0.66,P=0.043)。(2)吡格列酮组脾脏IFN-γmRNA相对吸光度值显著低于对照组(0.16±0.07VS 0.53±0.26,P=0.017);而PPARγmRNA表达水平则高于对照组(0.91VS 0.25,P=0.016)。(3)12周龄NOD鼠脾细胞吡格列酮组PPARγ活性高于对照组(0.05±0.01VS 0.02±0.01,P=0.006)。结论吡格列酮可通过活化PPARγ,下调IFN-γmRNA的表达,使Th细胞向Th1方向分化减少,减轻NOD鼠胰岛炎。更多还原

【Abstract】 Objective To investigate the mechanism of pioglitazone preventing insulitis and the role of peroxisome proliferator-activated receptor γ(PPARγ) on NOD mice.Methods Female NOD mice at 4 weeks of age were randomly divided into pioglitazone group(n=15) and control group(n=15).Pancreas were removed from NOD mice at 12 weeks of age in each group to score insulitis severity by routine H-E staining.Their spleens were for total RNA and nuclear proteins extraction.IL-4,IFN-γ and PPARγ mRNA levels in spleens were tested by RT-PCR.The activity of PPARγ nuclear protein in spleens was measured by ELISA.Results At 12 weeks of age,the insulitis score in pioglitazone group was lower than that in control group(1.79±0.75 VS 2.38±0.66,P = 0.043).IFN-γ mRNA level in pioglitazone group was lower than that in control group(0.16±0.07 VS 0.53±0.26,P=0.017),and PPARγ mRNA level in pioglitazone group was higher than that in control group(0.91 VS 0.25,P=0.016).At 12 weeks of age,the spleen PPARγ nuclear protein activity in pioglitazone group was higher than that in control group(0.05±0.01 VS 0.02±0.01,P=0.006).Conclusion Pioglitazone activate PPARγ nuclear protein,downregulate IFN-γ,diminish Th cells deviating to Th1,and prevents insulitis in NOD mice.更多还原