Abstract
Background and objective Anaesthetic preconditioning (APC) protects against myocardial ischaemia/reperfusion injury. Nuclear factor-κB (NF-κB) 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-κB 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-κB inhibitor parthenolide (PTN) was used before or after exposure to sevoflurane (PTNRAPC group and APCRPTN 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-κB p50/p65 before ischaemia (51±4/26±3% vs. 15±1/ 11±1% in the control group, P<0.05). After reperfusion, NF-κB 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-κB acted not only as a trigger but also as a mediator that played an important role in APC through upregulation of NF-κB 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-α during reperfusion, ultimately decreasing caspase-3 expression and apoptosis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 747-756 |
| Number of pages | 10 |
| Journal | European Journal of Anaesthesiology |
| Volume | 27 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2010 |
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Keywords
- Ischaemia/reperfusion
- Nuclear factor-κB
- Preconditioning
- Sevoflurane
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine
Cite this
Role of nuclear factor-κB in volatile anaesthetic preconditioning with sevoflurane during myocardial ischaemia/reperfusion. / Wang, Chen; Xie, Hong; Liu, Xia; Qin, Qin; Wu, Xuemei; Liu, Hong; Liu, Chunfeng.
In: European Journal of Anaesthesiology, Vol. 27, No. 8, 08.2010, p. 747-756.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of nuclear factor-κB in volatile anaesthetic preconditioning with sevoflurane during myocardial ischaemia/reperfusion
AU - Wang, Chen
AU - Xie, Hong
AU - Liu, Xia
AU - Qin, Qin
AU - Wu, Xuemei
AU - Liu, Hong
AU - Liu, Chunfeng
PY - 2010/8
Y1 - 2010/8
N2 - Background and objective Anaesthetic preconditioning (APC) protects against myocardial ischaemia/reperfusion injury. Nuclear factor-κB (NF-κB) 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-κB 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-κB inhibitor parthenolide (PTN) was used before or after exposure to sevoflurane (PTNRAPC group and APCRPTN 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-κB p50/p65 before ischaemia (51±4/26±3% vs. 15±1/ 11±1% in the control group, P<0.05). After reperfusion, NF-κB 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-κB acted not only as a trigger but also as a mediator that played an important role in APC through upregulation of NF-κB 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-α during reperfusion, ultimately decreasing caspase-3 expression and apoptosis.
AB - Background and objective Anaesthetic preconditioning (APC) protects against myocardial ischaemia/reperfusion injury. Nuclear factor-κB (NF-κB) 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-κB 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-κB inhibitor parthenolide (PTN) was used before or after exposure to sevoflurane (PTNRAPC group and APCRPTN 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-κB p50/p65 before ischaemia (51±4/26±3% vs. 15±1/ 11±1% in the control group, P<0.05). After reperfusion, NF-κB 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-κB acted not only as a trigger but also as a mediator that played an important role in APC through upregulation of NF-κB 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-α during reperfusion, ultimately decreasing caspase-3 expression and apoptosis.
KW - Ischaemia/reperfusion
KW - Nuclear factor-κB
KW - Preconditioning
KW - Sevoflurane
UR - http://www.scopus.com/inward/record.url?scp=77956842583&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956842583&partnerID=8YFLogxK
U2 - 10.1097/EJA.0b013e32833bb3ba
DO - 10.1097/EJA.0b013e32833bb3ba
M3 - Article
VL - 27
SP - 747
EP - 756
JO - European Journal of Anaesthesiology
JF - European Journal of Anaesthesiology
SN - 0265-0215
IS - 8
ER -