机构:[1]Department of Anaesthesiology, the Second Affiliated Hospital of Soochow University, and Institute of Neuroscience, Soochow University[2]Department of Anesthesiology, the Second Affiliated Hospital of Soochow University, Suzhou, China[3]Department of Anaesthesiology and Pain Medicine, University of California Davis Health System, Sacramento, California, USA[4]Department of Neurology, the Second Affiliated Hospital of Soochow University, and Institute of Neuroscience, Soochow University, Suzhou, China
Background and objective Anaesthetic preconditioning (APC) protects against myocardial ischaemia/reperfusion injury. Nuclear factor-kappa B (NF-kappa B) has been implicated in APC-induced myocardial protection in vitro. Our study tested the hypothesis that in-vivo APC with sevoflurane is triggered by NF-kappa B through downregulation of inflammatory mediators and upregulation of antiapoptosis factors to prevent myocardial injury during ischaemia/reperfusion. Methods In this in-vivo study, rats were anaesthetized and maintained with sodium pentobarbital throughout the experiment. Rats were exposed to 30 min of 2.5% sevoflurane followed by 15 min washout (APC group) or no inhalation anaesthetics (ischaemia/reperfusion group) before ischaemia/reperfusion. In the sevoflurane group, rats were exposed to 30 min sevoflurane followed by a 165 min washout period. The NF-kappa B inhibitor parthenolide (PTN) was used before or after exposure to sevoflurane (PTN+APC group and APC+PTN group). Left ventricular samples were obtained to measure infarct size, pro-inflammation and apoptosis. A P value less than 0.05 was considered significant. Results APC reduced infarct size (34 +/- 6%) compared with ischaemia/reperfusion (53 +/- 6%, P < 0.05). PTN administered before or after APC abolished the cardioprotection (53 +/- 5 and 52 +/- 7%, respectively, P < 0.05). APC decreased the myocardium apoptosis compared with the ischaemia/reperfusion only group (6 +/- 1 vs. 19 +/- 3%, P < 0.05); PTN administered before or after sevoflurane preconditioning abolished this effect. APC induced upregulation of NF-kappa B p50/p65 before ischaemia (51 +/- 4/26 +/- 3% vs. 15 +/- 1/11 +/- 1% in the control group, P < 0.05). After reperfusion, NF-kappa B was upregulated in the ischaemia/reperfusion and APC groups, but it was lower in the APC group than in the ischaemia/reperfusion group. PTN administered before and after APC inhibited the expressions. Before ischaemia, Bcl-2 was increased in the APC and sevoflurane groups (94 +/- 3 and 102 +/- 4%, respectively) compared with the control group (68 +/- 2%, P < 0.05). After reperfusion, intercellular adhesion molecule-1, tumour necrosis factor-a and caspase-3 expressions were significantly increased in the ischaemia/reperfusion group (92 +/- 5, 115 +/- 4 and 65 +/- 2% compared with the control group, P < 0.05); these increases were blunted in the APC group. Conclusion APC with sevoflurane produced myocardial protection against ischaemia/reperfusion in vivo. NF-kappa B acted not only as a trigger but also as a mediator that played an important role in APC through upregulation of NF-kappa B and the antiapoptosis protein Bcl-2 during the preconditioning period and then through downregulation of the inflammatory proteins intercellular adhesion molecule-1 and tumour necrosis factor-alpha during reperfusion, ultimately decreasing caspase-3 expression and apoptosis. Eur J Anaesthesiol 2010; 27:747-756
基金:
The present study was supported by grant no. 30872453 (to C.W.)
from the National the Natural Science Foundation of China, no.
BK2008166 (to C.W.) from the Natural Science Foundation of
Jiangsu Province, no. 2008–11 (to C.W.) from the Technology
Bureau of Suzhou, China, and no. 08KJD320005 (to H.X.) from
the Natural Science Research Projects of Colleges and Universities
in Jiangsu Province, China.
第一作者机构:[1]Department of Anaesthesiology, the Second Affiliated Hospital of Soochow University, and Institute of Neuroscience, Soochow University
通讯作者:
通讯机构:[*]Department of Anaesthesiology, the Second Affiliated Hospital of Soochow University, 1055, Sanxiang Road, Suzhou 215004, China
推荐引用方式(GB/T 7714):
Chen Wang,Hong Xie,Xia Liu,et al.Role of nuclear factor-kappa B in volatile anaesthetic preconditioning with sevoflurane during myocardial ischaemia/reperfusion[J].EUROPEAN JOURNAL OF ANAESTHESIOLOGY.2010,27(8):747-56.doi:10.1097/EJA.0b013e32833bb3ba.
APA:
Chen Wang,Hong Xie,Xia Liu,Qin Qin,Xuemei Wu...&Chunfeng Liu.(2010).Role of nuclear factor-kappa B in volatile anaesthetic preconditioning with sevoflurane during myocardial ischaemia/reperfusion.EUROPEAN JOURNAL OF ANAESTHESIOLOGY,27,(8)
MLA:
Chen Wang,et al."Role of nuclear factor-kappa B in volatile anaesthetic preconditioning with sevoflurane during myocardial ischaemia/reperfusion".EUROPEAN JOURNAL OF ANAESTHESIOLOGY 27..8(2010):747-56