Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.
Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.
复制标题
高迁移率族box-1蛋白的迷走神经调节介导电针诱导的缺血再灌注损伤中的心脏保护作用。
DOI：
10.1038/srep15503
复制
发表时间：
2015-10-26
影响因子：
4.6
通讯作者：
Song JG
中科院分区：
文献类型：
--
作者：
Zhang J;Yong Y;Li X;Hu Y;Wang J;Wang YQ;Song W;Chen WT;Xie J;Chen XM;Lv X;Hou LL;Wang K;Zhou J;Wang XR;Song JG
缺血心肌细胞过度释放高迁移率族蛋白1（HMGB1）激活炎症级联反应，增强再灌注后心肌损伤。电针内关穴可抑制心肌缺血后HMGB1的上调，减轻再灌注时的炎症反应和心肌损伤。电针的这些益处通过向小鼠施用重组HMGB1而部分逆转，并且通过施用抗HMGB1抗体而进一步增强。单侧迷走神经切断术或给予烟碱受体拮抗剂可显著降低电针对HMGB1释放的抑制作用，但化学交感神经切除术则无此作用。胆碱酯酶抑制剂新斯的明模拟电针对HMGB1释放和心肌缺血再灌注损伤的影响。用分离的新生心肌细胞进行的培养实验表明，乙酰胆碱，而不是去甲肾上腺素，通过α 7 nAchR依赖性途径抑制缺氧诱导的HMGB1释放。这些结果表明，电针通过迷走神经及其烟碱受体介导的信号传导抑制缺血心肌细胞HMGB1的释放。这有助于减轻再灌注期间的促炎反应和心肌损伤。
Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a α7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion.