肥大心肌细胞能量代谢途径变化及药物干预效应研究

目的 探讨肥大心肌细胞能量代谢途径变化及药物干预的作用。方法 应用血管紧张素Ⅱ（angiotensin Ⅱ，Ang Ⅱ，0．1μmol／L）加去甲肾上腺素（norepinephrine，NE 1μmol／L）诱导培养大鼠心肌细胞肥大，以同位素液闪计数法测定丙酮酸脱氢酶（pyruvate dehydrogenase，PDH）、肉碱脂酰转移酶-1（carnitine palmitoyhransferase 1，CPT-1）活性，以及葡萄糖有氧氧化率、葡萄糖酵解率和脂肪酸有氧氧化率。结果 （1）与正常心肌细胞比较，肥大心肌细胞总的PDH活性没有明显改变，但活化型PDH活性和葡萄糖氧化代谢率（glucose oxidation rate，GOR）显著增强，CPT-1活性和脂肪酸有氧氧化代谢率（fatty acid oxidationrate，FOR）显著降低；（2）与对照肥大心肌细胞比较，二氯乙酸（dichloroacetate，DCA 1000～10000mmol／L）和曲美他嗪（Trimetazidine，TMZ 1～5mmol／L）呈剂量依赖性的升高PDH活性和GOR，抑制CPT-1活性、FOR和葡萄糖酵解率（glucolysis rate，GLR）；（3）与对照肥大心肌细胞比较，抗霉素A（antimycin A，0．1～10mmol／L）呈剂量依赖性的抑制PDH活性和GOR和GLR，增强CPT-1活性和FOR；（4）二氯乙酸（1000mmol／L）加曲美他嗪（1mmol／L）可更有效刺激PDH活性和GOR，抑制CPT-1活性、FOR和GLR。结论 肥大心肌细胞能量代谢向糖代谢转化，DCA和TMZ均可进一步增强糖有氧氧化代谢抑制脂肪酸代谢。

Changes of energy metabolic pathway of hypertrophic cardiomyocytes and effect of intervening with drugs

Objective To investigate the changes of energetic metabolism of hypertrophic cardiomyocytes and the therapeutic effects of some drugs regulateing the energy metabolic pathway.Methods Cultured rat cardiomyocytes were induced to be hypertrophy by angiotensin II(Ang II) and norepinephrine(NE).The activity of pyruvate dehydrogenase(PDH),carnitine palmitoyltransferase 1(CPT-1),glucose oxidation rate(GOR),glucolysis rate(GLR) and fatyy acid oxidation rate(FOR) were determined by liquid scintillation counting.Results(1)The activity of the active PDH and GOR of hypertrophic cardiocytes increased but its activity of CPT-1 and FOR decreased significantly compared with the normal cardiocytes.(2)Compared with the control hypertrophic cardiomyocytes,the activity of the active PDH and GOR of hypertrophic cardiocytes were stimulated and its activity of CPT-1 and FOR and GLR were inhibited by DCA(1-10mmol/L)and TMZ(1-5mmol/L) respectively in dose-dependent manner.(3)Compared with the control hypertrophic cardiomyocytes,the activity of the active PDH and GOR of hypertrophic cardiocytes were inhibited but its activity of CPT-1 and FOR and GLR were stimulated by antimycin A(0.1~10mmol/L)in dose-dependent manner.(4)The activity of the active PDH and GOR of hypertrophic cardiocytes were stimulated and its activity of CPT-1 and FOR and GLR were inhibited more effectively by DCA(1mmol/L)combined with TMZ(1mmol/L)when compared with hypertrophic cardiomyocytes incubated with DCA(1mmol/L)and TMZ(1mmol/L)respectively.Conclusion The glucose oxidation increased and fatty oxidation decreased in hypertrophic cardiomyocytes,and it could be enhanced effectively by DCA and TMZ.