目的评价钠-钙交换体选择性抑制剂Sn-6对钙矛盾处理造成离体灌注大鼠心脏功能障碍和心肌细胞死亡的影响。方法离体心脏先后经历3 MIn无钙液、30 MIn有钙液灌注即钙矛盾处理,实验同步监测左室功能,并检测复钙期冠脉流出液乳酸脱氢酶(ldH)含量与实验结束时存活心肌组织面积的大小。结果钙矛盾处理使得左室功能丧失,表现为左室舒张末压(lVEdP)显著抬高,左心室发展压(lVdP)、心室压力变化最大速率(±dP/dT)为0;心脏几乎不存在活性组织;于无钙液灌注前2 MIn、无钙液灌注期和复钙后前5 MIn给予10μMOl/l Sn-6处理后,lVEdP显著降低,lVdP和±dP/dT明显恢复,心肌损伤面积缩小,ldH释放减少;Sn-6处理的对照心脏于灌流结束时左室功能没有显著改变。结论 Sn-6具有减轻钙矛盾处理造成的心功能损害,增加细胞存活的作用,提示钠-钙交换体是钙矛盾损伤的关键分子。Objective The present study was to observe the effect of sodium /calcium exchanger inhibitor SN-6 on heart dysfunction and cell death induced by calcium paradox.Methods Calcium paradox in isolated heart was elicited by 3-min calcium depletion followed by 30-min calcium repletion in the absence or presence of 10 μmol/L SN-6,an inhibitor of sodium/calcium exchanger.Cardiac function was monitored,and lactate dehydrogenase(LDH) release during calcium repletion and infarct size was measured.Results Upon calcium repletion,the heart deteriorated,exhibiting a marked depression in cardiac function,an enlarged infarct size and an increase in LDH release.These changes were significantly attenuated by SN-6.SN-6 had no effect on cardiac performance at the end of perfusion under control conditions.Conclusion The results demonstrate that SN-6 rescues heart dysfunction and cell death in calcium paradox.It also indicates that sodium/calcium exchanger is a key molecule in the injury.国家自然科学基金(30971196
