Remote ischaemic preconditioning involves signalling through the SDF-1α/CXCR4 signalling axis
Remote ischaemic preconditioning involves signalling through the SDF-1α/CXCR4 signalling axis
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DOI：
10.1007/s00395-013-0377-6
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发表时间：
2013-09-01
影响因子：
9.5
通讯作者：
Yellon, Derek M.
中科院分区：
文献类型：
--
作者：
Davidson, Sean M.;Selvaraj, Pradeep;Yellon, Derek M.
缺血预处理是已知的最有效的减少缺血和再灌注后梗死面积的实验方法之一。远程缺血性条件反射（RIC）现象引起了人们的极大兴趣，在该现象中，将预处理刺激施加到远离心脏的肢体，通过一种未知的体液因子刺激心脏保护，该体液因子被认为是3.5至15 kDa之间的蛋白质。基质细胞衍生因子-1（SDF-1 alpha或CXCL 12）是一种10 kDa的趋化因子，由缺氧诱导并招募干细胞，但也通过其受体CXCR 4发挥直接的急性心脏保护作用。血清二肽酶DPPIV切割并灭活SDF-1 α。我们测量了大鼠血浆中的SDF-1 α，发现RIC显著增加。DPPIV活性在RIC后没有变化，表明SDF-1 α的合成或释放增加导致血浆水平升高。AMD 3100是一种高度特异性的CXCR 4抑制剂，用于研究SDF-1 α参与RIC的假设。大鼠RIC将梗死面积从53 +/-3%降至27 +/-3%（n = 6，P < 0.05），在接受AMD 3100治疗的大鼠中被阻断（40 +/-4%）。RIC还改善了心脏乳头肌的功能恢复，这也被AMD 3100阻断。在该模型中，直接应用SDF-1 α被证实具有保护作用，并被AMD 3100阻断。RIC刺激SDF-1 α释放，这种10-kDa肽似乎是RIC机制所需的。
Ischaemic preconditioning is one of the most potent experimental modalities known to decrease infarct size after ischaemia and reperfusion. Much interest has been stimulated by the phenomenon of remote ischaemic conditioning (RIC), in which the preconditioning stimulus is applied to a limb remote from the heart to stimulate cardioprotection via an unidentified humoral factor, believed to be a protein between 3.5 and 15 kDa. Stromal cell-derived factor-1 (SDF-1 alpha or CXCL12) is a chemokine of 10 kDa that is induced by hypoxia and recruits stem cells, but also exerts direct, acute, cardioprotection via its receptor, CXCR4. The serum dipeptidase DPPIV cleaves and inactivates SDF-1 alpha. We measured SDF-1 alpha in rat plasma and found it was significantly increased by RIC. DPPIV activity was unchanged after RIC, suggesting that increased synthesis or release or SDF-1 alpha caused the increase in plasma levels. AMD3100, a highly specific inhibitor of CXCR4, was used to investigate the hypothesis that SDF-1 alpha is involved in RIC. RIC in rats, which decreased infarct size from 53 +/- 3 % to 27 +/- 3 % (n = 6, P < 0.05), was blocked in rats treated with AMD3100 (40 +/- 4 %). RIC also improved functional recovery of cardiac papillary muscle, and this, too, was blocked by AMD3100. Direct application of SDF-1 alpha was confirmed to be protective in this model and was blocked by AMD3100. RIC stimulates SDF-1 alpha release, and this 10-kDa peptide appears to be required for the mechanism of RIC.