反向钠钙交换体在大鼠心脏钙预处理中的作用

Reverse Mode Na^+/Ca^(2+) Exchanger Mediates the Cardioprotection of Ca^(2+) Preconditioning in Rat Heart

目的探讨钙预处理时反向钠钙交换体对抗钙矛盾损伤的作用及机制。方法25只SD大鼠随机等分为5组:正常对照(Control)组、钙矛盾(Ca PD)组、钙预处理(CPC)组、反向钠钙交换体抑制剂(KB-R7943)+CPC组和KB-R7943+Ca PD组。采用离体大鼠心脏Langendorff逆行灌注模型,观察各组心脏冠状动脉流量(CF)、左心室发展压(LVDP)、左心室内压变化速率(dp/dt)及冠状动脉循环流出液心肌肌钙蛋白I(cTnI)浓度的变化,HE染色观察各组心脏组织形态。结果与Ca PD组相比,CPC组CF、LVDP、dp/dt均显著提高(P<0.001),冠状动脉循环流出液中cTnI水平显著降低(P<0.001)。而钙预处理过程中加入反向钠钙交换体抑制剂KB-R7943,其心肌保护作用均被明显减弱(P<0.05)。结论钙预处理能够有效对抗钙矛盾对心肌造成的损伤,其机制涉及钙预处理时钠钙交换体反向交换活性的上调。

OBJECTIVE To investigate the role of reverse mode Na^＋/Ca^2 ＋ exchanger on the cardioprotection of calcium preconditioning （CPC）. METHODS The hearts of twenty - five SD rats were isolated, underwent Langendroff perfusion, and were randomized into 5 groups： （1） control group （65 rain perfusion with KH buffer）, （2） calcium paradox group （5 min perfusion with KH buffer lacking Ca^2＋ followed by 30 min KH buffer containing Ca^2＋ , Ca PD）, （3） calcium preconditioning group （5 cycles perfusion of 1 min Ca^2＋ depletion/5 min Ca^2＋ repletion ＋ Ca^2＋ PD,CPC）, （4） reverse mode Na ^＋/Ca^2 ＋ exchanger inhibitor KB - R7943 （3 μmol/L） ＋ CPC group （ addition of KB - R7943 during calci- um preconditioning）. （5） reverse mode Na^＋/Ca^2＋ exchanger inhibitor KB- R7943 （3 μmol/L） ＋Ca PD group （30 min perfusion with KH buffer containing KB - R7943 ＋ Ca PD）. Left ventricular developed pressure （LVDP）, rate of rise of left ventricular pressure （dp/dt）, coronary flow （CF）, and cardiac tropenin Ⅰ （cTnⅠ） release were measured. Sections with HE staining were analyzed to display the morphologic structures of the hearts. RESULTS The levels of LVDP,dp/dt, and CF of the CPC group were significantly higher than those of the Ca PD group （ all P 〈0. 001 ）. The release of cTnⅠ was reduced significantly in the CPC group as compared to the Ca PD group （ P 〈 0.001 ）. However, the improvement of the hemodynamics and the decrease in the cTnⅠ release elicited by calcium preconditioning were significantly attenuated by the reverse mode Na ^＋/Ca^2 ＋ exchanger inhibitor KB - R7943 employed during the whole process of the calcium preconditioning （ all P 〈 0.05 ）. CONCLUSION The enhancement of reverse mode Na^ ＋ exchanger was involved in the cardioprotection induced by calcium preconditioning in the isolated rat heart model.