The neural and humoral pathways in remote limb ischemic preconditioning
The neural and humoral pathways in remote limb ischemic preconditioning
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DOI：
10.1007/s00395-010-0099-y
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发表时间：
2010-09-01
影响因子：
9.5
通讯作者：
Hausenloy, Derek J.
中科院分区：
文献类型：
--
作者：
Lim, Shiang Y.;Yellon, Derek M.;Hausenloy, Derek J.
远程缺血预处理（RIPC）是一种治疗性干预，已被证明可以减少心肌损伤的临床设置。然而，潜在的心脏保护机制仍不清楚。我们假设RIPC利用体液和神经通路将心脏保护信号从预处理的远端器官传递到心脏。将C57 BL/6小鼠麻醉并进行体内30分钟冠状动脉缺血，随后进行120分钟心肌再灌注，在其结束时测量心肌梗塞大小并表示为风险区的百分比。通过3个周期的左股动脉闭塞5分钟，再灌注5分钟，然后再长时间心肌缺血，伴或不伴股静脉闭塞（体液途径），股神经切除术和/或坐骨神经切除术（神经途径）诱导RIPC。与对照组相比，RIPC组心肌梗死面积较小。然而，闭塞股静脉完全取消了RIPC的梗死限制作用。同样，股神经和坐骨神经联合切除也消除了RIPC的心脏保护作用。有趣的是，单独切除股神经或坐骨神经仅部分消除了RIPC的梗死限制作用。总之，远端肢体缺血预处理以一种涉及神经和体液途径的方式减少小鼠心肌梗死面积。
Remote ischaemic preconditioning (RIPC) is a therapeutic intervention that has been demonstrated to reduce myocardial injury in the clinical setting. However, the underlying cardioprotective mechanisms remain unclear. We hypothesised that RIPC utilises both humoral and neural pathways to convey the cardioprotective signal from the preconditioned remote organ to the heart. C57BL/6 mice were anaesthetised and subjected to in vivo 30 min coronary artery ischaemia followed by 120 min of myocardial reperfusion, at the end of which myocardial infarct size was measured and expressed as a percentage of the risk zone. RIPC was induced by 3 cycles of 5 min left femoral artery occlusion interspersed with 5 min reperfusion before prolonged myocardial ischaemia with or without femoral vein occlusion (humoral pathway), femoral nerve resection and/or sciatic nerve resection (neural pathway). RIPC resulted in a smaller myocardial infarct size when compared to control. However, occluding the femoral vein completely abolished the infarct-limiting effect of RIPC. Similarly, combined femoral and sciatic nerve resection also abolished the cardioprotective effect of RIPC. Interestingly, femoral nerve or sciatic nerve resection alone only partially abolished the infarct-limiting effect of RIPC. In conclusion, remote limb ischaemic preconditioning reduced myocardial infarct size in the mice in a manner which implicates both a neural and humoral pathway.