大鼠肥厚心肌线粒体ADP/ATP载体活性变化的实验研究

Changes of the Activity of ADP/ATP Carrier of Myocardial Mitochondria in Left Ventricular Hypertrophy Induced by Pressure Overload in Rats

目的探讨压力超负荷大鼠肥厚心肌线粒体内膜 ADP/ATP 载体(AAC)转运活性的变化。方法将雄性 SD 大鼠随机分为假手术组和腹主动脉缩窄组,术后5周及15周观察大鼠血流动力学参数、心室重构指标,密度梯度离心法提取大鼠心肌线粒体,用抑制剂终止法测定线粒体 AAC 的转运活性,高效液相色谱法测量心肌线粒体内腺苷酸含量。结果大鼠腹主动脉缩窄术后5周出现左心室肥厚,术后15周加重伴心功能减退;术后5周 AAC 活性降低,但无统计学意义,15周时 AAC 活性显著减低与线粒体内(ATP+ADP)含量下降相一致。结论压力超负荷后心功能减退的肥厚心肌 AAC 转运活性降低,使能量产生和利用异常,提示 AAC 活性改变是肥厚心肌组织能量代谢障碍及心功能减退的重要机制。

Objective To study the changes of activity of ADP/ATP carrier（AAC） of myocardial mitochondria in left ventricular hypertrophy induced by pressure overload in rats. Methods Male SD rats were randomly divided into 4 groups,coarctation of abdominal aorta 5 week group（ C5 group） , 15 weeks group（ C15 group） and sham operation group（ S5 , S15 group）. The hemodynamics and ventricular remod- eling parameter were measured. Mitochondria were isolated by centrifugation. The size of adenine acid pool （ATP, ADP, AMP） in mitochondria were measured by high performance liquid chromatography（HPLC）. The AAC activity was detected by the atractyloside - inhibitor stop technique. Results Left ventricular hypertrophy was observed in 5 weeks after coarctation and AAC activity reduced. Compare to sham operation,content of ATP,ADP and （ ATP ＋ ADP） in mitochondria decreased significantly in C1~ group, meanwhile a reduction of AAC activity was clearly observed and synchronous to reduction of mitochondria（ ATP ＋ ADP）. Condusion The change of AAC activity may derange mitochondrial oxidative phosphorylation during pressure overload and play a critical role in hypertrophy and disfunction of heart.