NF-κB p65、TNF-α对心肺复苏患者Nrf2/ARE 信号通路的影响
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摘要
目的通过对心肺复苏(CPR)患者血浆核转录因子kappa B(NF-κB)亚基p65、肿瘤坏死因子α(TNF-α)及核因子E2相关因子2(Nrf2)的相关性分析,研究NF-кB与Nrf2/ARE信号通路的关联性,并分析其对预后的影响。方法收集2015年7月—2017年7月杭州师范大学附属医院急诊科存活超过72 h的CPR患者,分别于心脏骤停(CA)时、自主循环恢复(ROSC)即刻、ROSC后2、8、12、24、48、72 h八个时间点采集其外周血,测定血浆中NF-κB亚基p65、TNF-α及Nrf2水平,观察其动态变化,并进行相关性分析,最后采用ROC曲线分析判断其对预后的影响。结果 100例CPR成功患者,36例存活超过72 h。Nrf2在CPR后出现不同程度的降低,在ROSC后8 h达到最低谷,而NF-κB亚基p65、TNF-α在CPR后均明显增高,分别在ROSC后12 h、8 h达到最高峰。Nrf2与NF-κB亚基p65、TNF-α呈负相关关系(r分别为-0.505、-0.446,P<0.05)。NF-κB亚基p65与TNF-α呈正相关关系(r=0.531,P<0.05)。ROC曲线分析提示NF-κB亚基p65、TNF-α可预测CPR患者预后的严重程度。结论 CA患者CPR后出现不同程度的炎症反应和氧化应激损伤,两者关系密切,互相影响,且炎症反应对预后的影响明显大于氧化应激损伤。
Objective To investigate the relevance between NF-κB signal pathway and Nuclear factor erythroid 2-related factor 2(Nrf2)/ARE signal pathway through analyzing the correlation among NF-κB p65, TNF-α and Nrf2 levels in cardiac arrest(CA) patients undergoing cardiopulmonary resuscitation(CPR). Methods Medical records of CA patients undergoing CPR and survived more than 72 hours were collected, the plasma levels of NF-κB p65, TNF-α and Nrf2 were tested at CA, return of spontaneous circulation(ROSC) and 2, 8, 12, 24, 48, 72 h after ROSC, their changes and correlations were analyzed. Furtherly, the factors affecting prognosis of CPR were analyzed by ROC curve. Results Total 36 patients survived more than 72 hours in 100 CA patients undergoing CPR and had ROSC. The plasma level of Nrf2 decreased to varying degrees, and dropped to the lowest level at 8 h after ROSC. However, the plasma levels of NF-κB p65 and TNF-α increased significantly, and peaked at 12 h and 8 h after ROSC respectively. Correlation analysis showed that Nrf2 was negatively correlated with NF-κB p65 and TNF-α(r=-0.505,-0.446, P<0.05), NF-κB p65 was positively correlated with TNF-α(r=0.531, P<0.05). ROC curve showed that NF-κB p65 and TNF-α could predict the prognosis of patients with CPR. Conclusion The inflammation and oxidative stress injury will occurred in CA patients undergoing CPR, they are closely related and affected each other. The effect of inflammation on prognosis is significantly greater than oxidative stress injury.
Objective To investigate the relevance between NF-κB signal pathway and Nuclear factor erythroid 2-related factor 2(Nrf2)/ARE signal pathway through analyzing the correlation among NF-κB p65, TNF-α and Nrf2 levels in cardiac arrest(CA) patients undergoing cardiopulmonary resuscitation(CPR). Methods Medical records of CA patients undergoing CPR and survived more than 72 hours were collected, the plasma levels of NF-κB p65, TNF-α and Nrf2 were tested at CA, return of spontaneous circulation(ROSC) and 2, 8, 12, 24, 48, 72 h after ROSC, their changes and correlations were analyzed. Furtherly, the factors affecting prognosis of CPR were analyzed by ROC curve. Results Total 36 patients survived more than 72 hours in 100 CA patients undergoing CPR and had ROSC. The plasma level of Nrf2 decreased to varying degrees, and dropped to the lowest level at 8 h after ROSC. However, the plasma levels of NF-κB p65 and TNF-α increased significantly, and peaked at 12 h and 8 h after ROSC respectively. Correlation analysis showed that Nrf2 was negatively correlated with NF-κB p65 and TNF-α(r=-0.505,-0.446, P<0.05), NF-κB p65 was positively correlated with TNF-α(r=0.531, P<0.05). ROC curve showed that NF-κB p65 and TNF-α could predict the prognosis of patients with CPR. Conclusion The inflammation and oxidative stress injury will occurred in CA patients undergoing CPR, they are closely related and affected each other. The effect of inflammation on prognosis is significantly greater than oxidative stress injury.
引文
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[15] 司金春,崔月,杨琰琦.亚低温治疗及选择时机对窒息大鼠心肺复苏后的脑保护作用[J].医学临床研究,2016,33(1):7-10.
[16] PAN X,YAN D,WANG D,et al.Mitochondrion-Mediated Apoptosis Induced by Acrylamide is Regulated by a Balance Between Nrf2 Antioxidant and MAPK Signaling Pathways in PC12 Cells[J].Mol Neurobiol,2017,54(6):4781-4794.
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[18] XING J,LU J.HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia[J].Cell Physiol Biochem,2016,39(2):511-520.
[19] WEI X,ZHANG B,ZHANG Y,et al.Hydrogen Sulfide Inhalation Improves Neurological Outcome via NF-κB-Mediated Inflammatory Pathway in a Rat Model of Cardiac Arrest and Resuscitation[J].Cell Physiol Biochem,2015,36(4):1527-1538.
[20] 崔喜梅,熊海霞,夏金明,等.乌司他丁对心肺复苏后Wistar鼠大脑皮层炎症反应的影响[J].中华急诊医学杂志,2015,24(1):33-37.
[2] 徐捷,龚秀芹.79例患者院前心跳呼吸骤停采取心肺复苏的临床分析[J].实用临床医药杂志,2016,20(24):15-19.
[3] SIAO F Y,CHIU C C,CHIU C W,et al.Managing cardiac arrest with refractory ventricular fibrillation in the emergency department: Conventional cardiopulmonary resuscitation versus extracorporeal cardiopulmonary resuscitation[J].Resuscitation,2015,92(7):70-76.
[4] BANSAL A,SINGH T,AHLUWALIA G,et al.Outcome and predictors of cardiopulmonary resuscitation among patients admitted in Medical Intensive Care Unit in North India[J].Indian J Crit Care Med,2016,20(3):159-163.
[5] SHAO F,LI C S,LIANG L R,et al.Outcome of out-of-hospital cardiac arrests in Beijing, China[J].Resuscitation,2014,85(11):1411-1417.
[6] XU J,SUN S,LU X,et al.Remote ischemic pre-and postconditioning improve postresuscitation myocardial and cerebral function in a rat model of cardiac arrest and resuscitation[J].Crit Care Med,2015,43(1):e12-18.
[7] ZHAO S,QIAN J,WANG J,et al.Effects of Oxygen Concentrations on Postresuscitation Myocardial Oxidative Stress and Myocardial Function in a Rat Model of Cardiopulmonary Resuscitation[J].Crit Care Med,2015,43(12):e560-566.
[8] LIN J Y,ZHANG M W,WANG J G,et al.Hydrogen sulfide improves neural function in rats following cardiopulmonary resuscitation[J].Exp Ther Med,2016,11(2):577-587.
[9] NEUMAR R W,SHUSTER M,CALLAWAY C W,et al.2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care[J].Circulation,2015,132(18 Suppl 2):S315-367.
[10] XIANG Y,ZHAO H,WANG J,et al.Inflammatory mechanisms involved in brain injury following cardiac arrest and cardiopulmonary resuscitation[J].Biomed Rep,2016,5(1):11-17.
[11] KRONICK S L,KURZ M C,LIN S,et al.Part 4:Systems of Care and Continuous Quality Improvement: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care[J].Circulation,2015,132(18 Suppl 2):S397-413.
[12] MOZAFFARIAN D,BENJAMIN E J,GO A S,et al.Heart disease and stroke statistics-2015 update:a report from the American Heart Association[J].Circulation,2015,131(4):e29-322.
[13] SHAO F,LI C S,LIANG L R,et al.Incidence and outcome of adult in-hospital cardiac arrest in Beijing,China[J].Resuscitation,2016,102(1):51-56.
[14] 冯璐,马青变.心肺复苏后患者神经功能预后的预测策略研究进展[J].中华急诊医学杂志,2016,25(10):1341-1344.
[15] 司金春,崔月,杨琰琦.亚低温治疗及选择时机对窒息大鼠心肺复苏后的脑保护作用[J].医学临床研究,2016,33(1):7-10.
[16] PAN X,YAN D,WANG D,et al.Mitochondrion-Mediated Apoptosis Induced by Acrylamide is Regulated by a Balance Between Nrf2 Antioxidant and MAPK Signaling Pathways in PC12 Cells[J].Mol Neurobiol,2017,54(6):4781-4794.
[17] VRIEND J,REITER R J.The Keap1-Nrf2-antioxidant response element pathway: a review of its regulation by melatonin and the proteasome[J].Mol Cell Endocrinol,2015,401(2):213-220.
[18] XING J,LU J.HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia[J].Cell Physiol Biochem,2016,39(2):511-520.
[19] WEI X,ZHANG B,ZHANG Y,et al.Hydrogen Sulfide Inhalation Improves Neurological Outcome via NF-κB-Mediated Inflammatory Pathway in a Rat Model of Cardiac Arrest and Resuscitation[J].Cell Physiol Biochem,2015,36(4):1527-1538.
[20] 崔喜梅,熊海霞,夏金明,等.乌司他丁对心肺复苏后Wistar鼠大脑皮层炎症反应的影响[J].中华急诊医学杂志,2015,24(1):33-37.