无创性肢体缺血预处理对缺血心肌的保护作用

Mechanism of cardioprotection induced by noninvasive limb ischemic preconditioning

目的验证在远距离预处理中抑制线粒体钙单向转运体对缺血、再灌注心肌的保护作用。方法结扎冠脉左前降支使心脏局部缺血30min，然后再灌注120min形成缺血／再灌注损伤模型。分别应用远距离预处理、线粒体钙单向转运体抑制剂（钌红）、线粒体钙单向转运体激动剂（精胺、SB202190）进行干预。远距离预处理采用右股动脉结扎5min，再灌注5min，反复3个循环实现。再灌注过程中测量平均动脉压，心率，血浆乳酸脱氢酶水平，结束后测量心肌梗死面积。结果与缺血再灌注组相比，远距离预处理使再灌注后心肌梗死面积缩小[（20．4±2．5）％比（51．0±6．0）％]，乳酸脱氢酶的释放减少[（271±9）U／L比（339±39）U／L]；而在远距离预处理前给予精胺或SB202190干预后梗死面积、乳酸脱氢酶降幅均减小，分别为[（40．8±9．2）％，（383±43）U／L；（44．3±6．8）％，（356±26）U／L]。结论远距离预处理通过抑制线粒体钙单向转运体的开放可以减轻缺血／再灌注对缺血心肌的损伤，起到对缺血心肌的保护作用。

Objective To verify the inhibitory effect of mitochondrial calcium uniporter in remote preconditioning-induced cardioprotection. Methods By occlusion and reperfusion of left anterior descending artery, the rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vivo. Thus the ischemic reperfusion model was established. The rats were randomly assigned to undergo one of the following maneuvers： （1） remote preconditioning; （2） ruthenium red （an inhibitor of mitochondrial calcium uniporter）; （3） spermine or SB202190 （an opener of mitochondrial calcium uniporter） . Remote preconditioning was elicited by three cycles of 5 min of right femoral artery occlusion interspersed with 5 min of reperfusion. The mean arterial blood pressure, heart rate and lactate dehydrogenase released in plasma were measured during reperfusion but the infarct size was measured after reperfusion. Results In comparison with I/R group, remote preconditioning limited infarct size [ （20.4 ± 2. 5 ）% vs （51.0± 6. 0）% ] and lactate dehydrogenase release [ （271±9）U/L vs （339 ±39） U/L] during reperfusion. On the contrary, spermine or SB202190 attenuated the reduction of infarct size and lactate dehydrogenase release induced by remote preconditioning. The group of spermine was [ （40. 8±9. 2）% vs （20. 4±2. 5）% ] and [（383±43） U/L vs （271 ±9） U/L] while the group of SB202190 was [（44.3±6.8）% vs （20.4± 2.5）%] and[（356±26）U/L vs（271 ±9） U/L]. Conclusion Inhibition of mitochondrial calcium uniporter opening is involved in the remote preconditioning-induced cardioprotection.