Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.
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.
Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.|Department of Anesthesiology, The first Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Juan
J
Zhang
Laboratory of Integrative Medical Surgery Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Yue
Y
Yong
Laboratory of Integrative Medical Surgery Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Xing
X
Li
Department of Anesthesiology, 452nd Hospital of the People's Liberation Army, Chengdu 610061, China.
Yu
Y
Hu
Department of Anesthesiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Jian
J
Wang
Department of Anesthesiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Yong-Qiang
YQ
Wang
Department of Anesthesiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Wei
W
Song
Department of Anesthesiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Wen-Ting
WT
Chen
Department of Anesthesiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Jian
J
Xie
Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Xue-Mei
XM
Chen
Department of Anesthesiology, Shanghai Pneumology Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
Xin
X
Lv
Department of Nursing, Shanghai Pneumology Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
Li-Li
LL
Hou
Laboratory of Integrative Medical Surgery Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Ke
K
Wang
Department of Cardiothoracic Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Jia
J
Zhou
Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Xiang-Rui
XR
Wang
Department of Anesthesiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Jian-Gang
JG
Song
D000818:Animals; D015671:Electroacupuncture; D024243:HMGB1 Protein / Q000502:physiology*; D051379:Mice; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000517:prevention & control*
D024243:HMGB1 Protein