胰岛素对单核细胞PPARγ配体结合转录活性的影响  

Insulin Regulates Ligand-Dependent Transcriptional Activity of PPARγ in Monocytes

作　　者：葛恒[1] 张俊峰[1] 郭秉诗[2] 王长谦[1] 

机构地区：[1]上海第二医科大学仁济医院心内科,上海200001 [2]上海第二医科大学上海市健康科学中心细胞分子医学实验室

出　　处：《上海第二医科大学学报》2005年第9期894-897,共4页Acta Universitatis Medicinalis Secondae Shanghai

基　　金：国家自然科学基金(30070869)资助项目.

摘　　要：目的探讨胰岛素对单核细胞中PPARγ配体结合转录活性的影响。方法在人类单核细胞系U937细胞中共转染PPARγ表达载体和PPARγ报告载体,后者表达虫荧光素酶,其启动子中含有PPARγ结合位点(PPRE),细胞表达虫荧光素酶的量受PPARγ配体结合转录活性决定,裂解细胞加入虫荧光素酶底物后,所产生的荧光强度即代表PPARγ的配体结合转录活性。结果共转染细胞加入已知PPARγ的配体吡格列酮后显著激活PPARγ的配体结合转录活性,使荧光强度增强4.53倍(P<0.001),而在加入吡格列酮同时加入胰岛素,荧光强度明显减弱,0.5μmol/L胰岛素使荧光值降低(21±6)%(P=0.024);1μmol/L的胰岛素则使荧光强度降低(41±7)%(P=0.006);胰岛素作用呈剂量依赖性(P=0.029)。结论胰岛素在单核细胞中显著抑制PPARγ的配体结合转录活性。Objective To investigate whether high dose insulin can inhibit ligand-dependent transcriptional activity of peroxisome proliferator-activated receptor （PPAR） in monocytes. Methods Co-transfect human monocytic line U937 cells with PPARγ expression vector and PPARγ reporter vector by electroporation. The PPARγ reporter vector had sequence coding for lueiferase which was under the control of the promoter that contained the binding site for activated PPARγ （PPAR response element, PPRE） so that the expression of luciferase in cells was determined by the ligand-dependent transcriptional activity of PPARγ, while adding the substrate of luciferase into the lysis of the transfected cells, fluorescence detected presented the ligand-dependent transcriptional activity of PPARγ. Results The known PPARγ ligaud pioglitazone greatly activated PPARγ transcriptional activity, resulting in a 4.53-fold increase in luciferase activity （ P 〈0. 0.01 ） ; simultaneous treatment of 0.5 μmol/L and 1 μmol/L insulin significantly decreased luciferase activity by （21 ±6）% （P=0.024）and （41 ±7） % （P=0.006）, respectively; the inhibitory effect of insulin was dose dependent （ P = 0. 029 ）. Conclusion Insulin can effectively inhibit the liganddependent transcriptional activity of PPARγ in monocytes.

关 键 词：胰岛素 单核细胞 过氧化物酶体增殖剂激活受体γ 动脉粥样硬化 炎症 

分 类 号：R543.5[医药卫生—心血管疾病]