中国病理生理杂志Issue(7)：1160-1165,6.DOI:10.3969/j.issn.1000-4718.2015.07.002
PPARα／PGC-1α在阿霉素扩张型心肌病小鼠心肌组织中的表达及作用
Role of PPARα/PGC-1αin doxorubicin induced mouse dilated cardio-myopathy
摘要
Abstract
[ ABSTRACT] AIM:To investigate the changes of peroxisome proliferator-activated receptors ( PPAR)α/peroxi-some proliferator activated receptor coactivator 1 alpha ( PGC-1α) in doxorubicin ( DOX) induced dilated cardiomyopathy ( DCM) and its effect on the energy metabolism and myocardial function in mice .METHODS:Forty mice were randomly divided into 4 groups:control group, DOX group, PPARαinhibitor group and PPARαagonist group.The DCM model was established by injection of DOX.The protein levels of PPARα/PGC-1αwere detected.The PPARαinhibitor and PPARαagonist were used 2 weeks beforeinjection of DOX.The contents of adenine acid and phosphocreatine ( Pcr) in the mito-chondria were measured by high-performance liquid chromatography ( HPLC) .The ANT activity was analyzed by the atrac-tyloside-inhibitor stop technique.The changes of the echocardiography and hemodynamics were also observed.RESULTS:DOX induced DCM model was successfully established.The protein levels of PPARαand PGC-1αin control group were significantly higher than those in DOX group (P<0.05).Both of the high-energy phosphate contents and the transport ac-tivity of ANT were decreased in DOX group (P<0.05), and the hemodynamic parameters were disordered (P<0.01). Compared with DOX group, PPARαinhibitor pre-treatment significantly reduced the PPARα/PGC-1αexpression.Mean-while, high-energy phosphate contents in the mitochondria and the ANT transport activity of the mitochondria decreased, as well as the left ventricular function ( P<0.05) .On the other hand, PPARαagonist significantly increased the expression of PPARαand PGC-1α, and improved the transport activity of ANT.In addition, the hemodynamic parameters were amel-iorated, but the high-energy phosphate contents of the mitochondria did not significantly change.CONCLUSION:PPARα/PGC-1αplays an important role in the regulation of ANT transport activity in dilated cardiomyopathy induced by DOX, and the activation of PPARα/PGC-1αhas protective effects on the DCM induced by DOX.关键词
过氧化物酶体增殖物活化受体α/过氧化物酶体增殖物活化受体协同刺激因子1α/阿霉素/扩张性心肌病/能量代谢Key words
Peroxisome proliferator-activated receptorsα/Peroxisome proliferator activated receptor coactiva-tor 1α/Doxorubicin/Dilated cardiomyopathy/Energy metabolism分类
医药卫生引用本文复制引用
王学胜,杨永曜,杨天和,蒋清安..PPARα／PGC-1α在阿霉素扩张型心肌病小鼠心肌组织中的表达及作用[J].中国病理生理杂志,2015,(7):1160-1165,6.基金项目
国家自然科学基金资助项目 （）
