压力负荷性大鼠肥厚心肌过氧化物酶体增殖剂活化受体α(PPARα)和肉碱棕榈酰转移酶(MCPT-I)mRNA的表达变化

Expression of PPAR α and M-CPT-ImRNA in Cardiac Hypertrophy

目的 了解压力负荷性肥厚心肌PPARα和M CPT ImRNA的表达变化 ,探讨PPARα调控心肌线粒体脂肪酸摄取及维持能量和脂质平衡的作用。方法 观察大鼠腹主动脉缩窄术后 2、4、8、16周血流动力学参数、心室重塑指标、血清和心肌游离脂肪酸的含量及PPARα和M CPT ImRNA的表达变化。结果 随着肥厚程度的增加 ,压力负荷性大鼠血清和心肌游离脂肪酸蓄积增加 ,心肌PPARα和M CPT ImRNA的表达逐渐下调 ,而且与脂肪酸的利用下调相一致。结论 病理性肥厚心肌能量代谢底物发生改变 ,脂肪酸氧化不占主导地位 ;PPARα在转录水平上失活 ,对心肌线粒体脂肪酸摄取起重要的调控作用 ;

Objective To study the expression of PPAR α and M CPT I mRNA in cardiac hypertrophy and the regulation effect of PPAR α on mitochondrial fatty acid uptake. Methods Using a model of cardiac hypertrophy induced by coarctation of abdominal aorta(CAA) in male Wistar rats, hemodynamics, ventricular remodeling parameters, free fatty acid in blood serum and cardiac myocyte and expression of PPAR α and M CPT I mRNA were investigated 2, 4, 8, 16 weeks after operation and sham operation. Results Cardiac PPAR α and M CPT I gene expression were decreased, meanwhile the accumulation of free fatty acid and a reduction in uptake of fatty acid in myocardium were manifested in the development of cardiac hypertrophy. Conclusion The metabolic substrate in hypertrophic myocardium underwent substantial changes. Fatty acid oxidation appears not to be a major substrate of energy metabolism in cardiac hypertrophy. PPAR α is deactivated at transcriptional level and plays a key role on mitochondrial import of fatty acids in myocardial, leading to diminish in myocardial lipid and energy homeostasis.