摘要
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.
出处
《中国体外循环杂志》
2008年第1期36-39,共4页
Chinese Journal of Extracorporeal Circulation
基金
国家"十一五"科技支撑计划(2006BAI01A08)
陕西省科技攻关项目(2007K14-05(10))
关键词
心脏
大鼠
钠钙交换体
钙预处理
钙矛盾
Heart
Rat
Na^+/Ca^2+ exchanger
Calcium preconditioning
Calcium paradox