压力超负荷致心室重构大鼠线粒体内腺苷酸转运体表达的改变

目的探讨压力超负荷致心室重构时大鼠心肌线粒体内膜腺苷酸转运体(ANT)表达的改变及其意义。方法雄性SD大鼠52只行腹主动脉缩窄术,随机分为腹主动脉缩窄5周组(A5w组)、腹主动脉缩窄15周组(A15w组)、假手术5周组(SH5w组)和假手术15周组(SH15w组)4组,每组13只大鼠,观察大鼠血流动力学参数、心室重构指标,密度梯度法提取大鼠心肌线粒体,高效液相色谱法测量心肌组织及线粒体腺苷酸含量,Western blot法分析心肌线粒体ANT表达。结果大鼠腹主动脉缩窄术后5周出现左心室肥厚,术后15周加重并有心功能减退;分别与同时间SH5w组和SH15w组比较,A5w组及A15w组心肌组织ATP、ADP含量均降低,A15w组线粒体内ATP及ADP含量降低;A15w组线粒体ANT表达降低,并与心肌线粒体内ATP及ADP含量变化相一致。结论心室重构伴心功能减退时,心肌线粒体ANT表达降低,导致细胞内腺苷酸分布异常,是肥厚心肌能量代谢障碍的重要机制。

Changes of expression of ANT in myocardium of left ventricular remodeling induced by pressure overload in rats

Objective To explore the changes of expression of adenine nucleotide translocator(ANT) in myocardium of left ventricular remodeling induced by pressure overload in rats and its significance.Methods Male SD rats were randomized into 4 groups:coarctation of abdominal aorta 5week group(A5 group),15week group(A15 group) and sham operation groups(SH5,SH15groups).The hemodynamics and ventriclar remodeling parameters were measured.Ventricle of heart was removed and mitochondria were isolated by centrifugation.The sizes of adenine nucleotide pools(ATP,ADP) in myocardium and mitochondria were measured by high performance liquid chromatography.The expression of ANT in mitochondria was detected by Western blot analysis.Results Left ventricular hypertrophy was observed in A5 group and was agravated in A15 group.Compared with sham operation groups,contents of ATP and ADP decreased significantly in myocardium of both A5 group and A15 group,and contents of ATP and ADP in mitochondria decreased in A15 group.The expression of ANT in mitochondria of myocardium decreaed in A15 group.Conclusion The expression of ANT was inhibited during development of pressure overload-induced left ventricular remodeling,leading to abnormal distribution of the adenine nucleotide in myocardial cells,which may play a critical role in disturbance of energy metabolism in hypertrophy and dysfunction of heart.