卡维地洛减弱肥厚心肌能量代谢向胚胎型转换的分子机制

目的 :观察压力负荷性大鼠肥厚心肌能量代谢的转换模式及卡维地洛的作用 ,探讨卡维地洛减弱压力负荷性心肌能量代谢胚胎型转换的分子调控机制。方法 :用卡维地洛治疗腹主动脉缩窄术后 4周的雄性 Waster大鼠 ,治疗 12周后观察假手术组、腹主动脉缩窄组和卡维地洛干预组大鼠血流动力学参数、心室重构指标、血清和心肌游离脂肪酸的含量及肌型肉毒碱棕榈酰转移酶 I（ M-CPT-I）和中链脂酰辅酶 A脱氢酶 （ MCAD） m RNA的表达变化。结果 :术后 16周大鼠左室心肌明显肥厚 ,血清和心肌游离脂肪酸的含量增加 ,左室肥厚心肌 M-CPT-I和MCAD m RNA的表达下调。卡维地洛治疗 12周后能够明显改善上述变化。结论 :压力负荷性大鼠肥厚心肌能量代谢模式发生胚胎型转换 ;卡维地洛能够减少左室心肌脂肪酸氧化限速酶和关键酶的基因表达 ,减弱心肌胚胎型能量代谢的转换

Molecular mechanism of Carvedilol on attenuating the reversion back towards fetal energy metabolism occurring with the development of cardiac hypertrophy

AIM: To study the reversion of the metabolic gene expression pattern of hypertrophic cardiac muscle and role of Carvedilol, and to explore the molecular regulation mechanism of Carvedilol on attenuating the reversion back towards fetal energy metabolism occurring with the development of cardiac hypertrophy. METHODS: A model of hypertrophy induced by coarctation of abdominal aorta(CAA) in male wistar rats was used to investigate the hemodynamics, ventricular remodeling parameters, free fatty acid in blood serum and cardiac myocyte and expressions of muscle carnitine palmitoyltransferase I( M CPT I)and medium chain acyl CoA dehydrogenase (MCAD) mRNA in the experimental animals at 16 week after operation(CAA) and sham operation(SH) and Carvedilol intervention group(CAR). RESULTS: The left ventricle showed significant hypertrophy 16 weeks after the operation, fatty acids accumulated significantly and levels of M CPT I and MCAD mRNA continued to be downregulated during hypertrophic growth. Carvedilol could attenuate these changes after 12 week therapy. CONCLUSION: Pressure overload downregulates expression of rate limiting enzyme and key enzyme of fatty acid oxidation, leading to the metabolic fetal switch of energy substrate. Carvedilol attenuates this reversion of the metabolic gene expression pattern towards fetal levels through up regulating expressions of M CPT I and MCAD mRNA.