吡格列酮对缺氧/复氧后新生大鼠心肌细胞线粒体膜电位的影响  

Effects of Pioglitazone on Mitochondrial Membrane Potential of Neonate Rat's Myocardial Cells after Hypoxia/Reoxygenation

作　　者：朱启伟[1] 王浩[1] 叶平[1] 骆雷鸣[1] 张今尧[1] 

机构地区：[1]中国人民解放军总医院老年心内二科,北京100853

出　　处：《四川大学学报（医学版）》2011年第6期784-788,共5页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(批准号30872713);北京市自然科学基金(7082083)资助

摘　　要：目的观察过氧化物酶体增殖物激活型受体γ(PPARγ)受体激动剂吡格列酮对缺氧/复氧后的大鼠心肌细胞线粒体膜电位的影响,探讨其可能的机制。方法原代培养的新生SD大鼠心肌细胞,经DMSO溶媒、不同浓度吡格列酮单独或联合PPARγ受体抑制剂GW9662及蛋白激酶C(protein kinase C,PKC)抑制剂Chelerythrine等预处理24h后,各组同时建立缺氧/复氧模型,经JC-1染色后用激光共聚焦显微镜检测线粒体膜电位(ΔΨm)。结果与未经缺氧处理的对照组相比,缺氧/复氧模型组心肌细胞红/绿荧光比率下降,差异有统计学意义(P<0.01);吡格列酮处理组与对照组相比,吡格列酮0.1μmol/L、1μmol/L和2μmol/L组红/绿荧光比率均下降,差异有统计学意义(P<0.01);与吡格列酮2μmol/L组相比,吡格列酮+GW9662组和吡格列酮+Chelerythrine组红/绿荧光比率下降,差异均有统计学意义(P<0.01)。结论心肌细胞缺氧/复氧后,细胞线粒体膜电位下降,吡格列酮具有对抗膜电位下降的作用,这种细胞保护作用可能通过激活PPARγ来实现,同时也可能与PKC途径有关。Objective To explore the effectiveness and mechanism of pioglitazone on mitochondrial membrane potential of neonate rat＇s myocardial cells after hypoxia/reoxygenation.Methods Primary cultured myocardial cells of neonate Sprague-Dawley rats were pretreated with different concentrations of pioglitazone,pioglitazone＇s inhibitor and Chelerythrine,an inhibitor of protein kinase C（PKC）.Hypoxia/reoxygenation model was established after 24 h of pretreatment.Subsequently,the mitochondrial membrane potential was detected with JC-1 staining under laser confocal microscopy during reoxygenation phase.Results Compared with the control group,red/green fluorescent ratio of myocardial cells in the H-r model group decreased significantly after hypoxia/reoxygenation（red/green fluorescent ratio reduced from 1.20±0.05 to 1.13±0.02,P0.01）,and also decreased in 0.1 μmol/L,1 μmol/L and 2 μmol/L pioglitazone group（1.11±0.01,1.10±0.01,1.16±0.03,P0.01,respectively）.The red/green fluorescent ratio in pioglitazone＋GW9662 group（1.12±0.02） and pioglitazone＋Chelerythrine group（1.07±0.01） were both significantly lower than those in 2 μmol/L pioglitazone group（P0.01）.Conclusion The mitochondrial membrane potential of neonate rat＇s myocardial cells was descend after hypoxia/reoxygenation,while pioglitazone can interrupt the process,indicating that the activation may be relevant to peroxisome proliferator-activated receptor gamma（PPARγ） ligand and PKC pathway.

关 键 词：过氧化物酶体增殖物激活型受体Γ 线粒体膜电位 激光共聚焦扫描显微镜 

分 类 号：R363[医药卫生—病理学]