婴幼儿体外循环炎症因子与S100蛋白的关系研究及临床意义的探讨
|
摘要
目的:体外循环(CPB)相关脑损伤是心脏直视手术后主要的并发症之一,严重者可导致死亡。CPB相关的严重脑损伤多与脑栓塞、颅内出血及各种意外有关。随着技术的进步,此类损伤逐渐减少。目前先心病手术向着小年龄、低体重、复杂畸形方向发展,炎症反应与脑损伤的关系渐为人所重视。CPB是一种非生理的循环方式,引发全身炎症反应,对中枢神经系统产生毒性损害。此类损伤多表现为亚临床过程,而不易早期发现。婴幼儿的中枢神经系统在形态与功能上均不成熟,与成年脑显著不同,更易受到影响,但如能早期发现并干预,则可逆性更强。CPB术后患儿由于辅助呼吸、血液动力学不稳定需镇静且早期不宜搬动,以及婴幼儿神经精神检查的特殊性,影响了对神经系统的观察,不利于损害的早期干预。而S100蛋白是目前反映脑组织损伤的最特异而敏感的生化标志物。本研究欲通过测定围CPB期细胞因子(TNF-α、IL-6、IL-8)与脑损伤标志物S100蛋白的变化及相关性,探讨婴幼儿体外循环中炎症反应与亚临床脑损害的关系,为临床的防治提供依据。
对象与方法: 3岁以下非紫绀型先心病接受手术治疗患儿40例分为2组,CPB组与非CPB组各20例。CPB组于术前(T1),停CPB后即刻(T2),30分钟(T3),2小时(T4),6小时(T5),24小时(T6),非CPB组于术前(t1),手术结束(t2),术后30分钟(t3), 2小时(t4),6小时(t5),24小时(t6)分别抽取桡动脉血4ml,离心分离出血清。采用酶联免疫吸附法测定血清TNF-α、IL-6、IL-8和S100蛋白含量。比较CPB组和非CPB组的变化趋势,并对TNF-α、IL-6、IL-8分别与S100做相关性分析。
Objective: Cerebral injury related to cardiopulmonary bypass (CPB) is one of the main complications after intracardiac surgery. The severe one could develop to death. Evident brain injuries are mostly caused by embolism, intracranial hemorrhage or various kinds of accidents. However, with the advance in technical competence, such injuries obviously declined. Nowadays, more and more infants with low weight, complicated malformation receive operation in early age. Therefore great attention is devoted to the correlation between inflammatory response and cerebral injury. Systemic inflammatory response stimulated by CPB that is one kind of unphysiologic circulation can do toxic damage on cerebral tissue. Such injuries mostly demonstrate subclinical process. Infant’s center nervous system (CNS) that is immature and differs from adult brain remarkably is easier injured. But these injuries can be reversible, if being monitored and interfered in early stage. It is difficult to inspect infant during the period of CPB for the effect of ventilation and sedative. Furthermore the specific characteristics of infant neurological examination and the difficulty to perform examinations such as CT, MRI, and EEG et al are also disadvantages. The neuroproteins S-100 released into the circulation are suggested to be reliable and sensitive biochemical markers for primary brain damage. The study was designed to test the serum levels of cytokines(TNF-α、IL-6、IL-8) and S-100 during the CPB. The objective is to investigate the trend of these targets and the correlation between inflammatory response in infant CPB and subclinical cerebral injury.
Methods: 40 infants no more than 3 years old with acyanotic
对象与方法: 3岁以下非紫绀型先心病接受手术治疗患儿40例分为2组,CPB组与非CPB组各20例。CPB组于术前(T1),停CPB后即刻(T2),30分钟(T3),2小时(T4),6小时(T5),24小时(T6),非CPB组于术前(t1),手术结束(t2),术后30分钟(t3), 2小时(t4),6小时(t5),24小时(t6)分别抽取桡动脉血4ml,离心分离出血清。采用酶联免疫吸附法测定血清TNF-α、IL-6、IL-8和S100蛋白含量。比较CPB组和非CPB组的变化趋势,并对TNF-α、IL-6、IL-8分别与S100做相关性分析。
Objective: Cerebral injury related to cardiopulmonary bypass (CPB) is one of the main complications after intracardiac surgery. The severe one could develop to death. Evident brain injuries are mostly caused by embolism, intracranial hemorrhage or various kinds of accidents. However, with the advance in technical competence, such injuries obviously declined. Nowadays, more and more infants with low weight, complicated malformation receive operation in early age. Therefore great attention is devoted to the correlation between inflammatory response and cerebral injury. Systemic inflammatory response stimulated by CPB that is one kind of unphysiologic circulation can do toxic damage on cerebral tissue. Such injuries mostly demonstrate subclinical process. Infant’s center nervous system (CNS) that is immature and differs from adult brain remarkably is easier injured. But these injuries can be reversible, if being monitored and interfered in early stage. It is difficult to inspect infant during the period of CPB for the effect of ventilation and sedative. Furthermore the specific characteristics of infant neurological examination and the difficulty to perform examinations such as CT, MRI, and EEG et al are also disadvantages. The neuroproteins S-100 released into the circulation are suggested to be reliable and sensitive biochemical markers for primary brain damage. The study was designed to test the serum levels of cytokines(TNF-α、IL-6、IL-8) and S-100 during the CPB. The objective is to investigate the trend of these targets and the correlation between inflammatory response in infant CPB and subclinical cerebral injury.
Methods: 40 infants no more than 3 years old with acyanotic
引文
1. Taylor KM. Central nervous system effects of cardiopulmonary bypass. Ann Thorac Surg, 1998,66(5suppl):S20-24.
2. 谢立刚, 胡小琴, 吴新民, 等. 心血管手术后早期神经精神并发症的调查. 中国循环杂志, 2001,16: 369-371.
3. Selnes OA, Goldsborough MA, Borowicz LM, et al. Neurobehavioural sequelae of cardiopulmonary bypass. Lancet, 1999, 353: 1601-1606.
4. Georgiadis D, Berger A, Kowatschev E, et al. Predictive value of S100βand neuron-specific enolase levels for adverse neurologic outcome after cardiac surgery. J Thorac Cardiovasc Surg. 2000, 119(1):138-147.
5. Mussack T, Biberthaler P, Kanz KG, et al. Immediate S-100B and neuron specific enolase plasma measurements for rapid evaluation of primary brain damage in alcohol-intoxicated, minor head-injured patients. Shock.. 2002, 18(5): 395-400.
6. Vingerhoets G, Van Nooten G, Vermassen F, et al. Short-term and long-term neuropsychological consequences of cardiac surgery with extracorporeal circulation. Eur J Cardiothorac Surg, 1997, 11(3): 424-431.
7. 吴万福, 胡长林. 炎性细胞因子在脑出血继发性脑损害中的作用. 国外医学脑血管疾病分册. 2005, 13(4):303-306.
8. 周建美, 邹定全, 常业恬. 体外循环心脏手术病人脑组织炎性细胞因子与脑损伤的关系. 中华麻醉学杂志, 2005, 25(12): 939-940.
9. 刘传绶, 董培青. 常温体外循环现状. 中华胸心血管外科杂志, 2000, 16(2): 116-118.
10. Morganti-Kossmann MC, Rancan M, Otto VI, et al. Role of cerebral inflammation after traumatic brain injury: a revisited concept. Shock, 2001, 16(3): 165-177.
11. Goto T, Baba T, Honma K, et al. Magnetic resonance imaging findings and postoperative neurologic dysfunction in elederly patients undergoing coronary artery bypass grafting. Ann Thorac Surg, 2001, 72(1):137-142.
12. Huang TL, Banion MK. Interleukin-1βand tumor necrosis factor-alpha suppress dexamethasone induction of glutamine synthetase in primary mouse astrocytes. J Neurochem, 1998,71(4): 1436-1442.
13. 高玲, 黄鹏, 潘慧, 祝世功. 促炎性细胞因子诱导 NF-κB 激活促进神经细胞凋亡机制. 中国病理生理杂志, 2005, 21(8):1648
14. Steinberg JB, Kapelanski DP, Olson JD, Weiler JM. Cytokine and complementlevels in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg, 1993;106(6):1008-1016.
15. LeMaire SA, Bhama JK, Schmittling ZC, et al. S100B correlates with neurologic complications after aortic operation using circulatory arrest. Ann Thorac Surg, 2001,71(6): 1913-1918.
16. Basile AM, Fusi C, Conti AA, et al. S100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study. Eur Neurol, 2001,45(3):151-159.
17. Ali MS, Harmer M, Vaughan R. Serum S100 protein as a maker of cerebral damage during cardiac surgery. British Journal of Anaesthesia, 2000, 85(2):287-298.
18. 程卫平, 杨九光. 体外循环围术期精神评价手段. 见: 龙村主编, 体外循环学. 北京, 人民军医出版社, 2004, 112
19. 高长青, 贺涛, 李伯君, 等. 非体外循环与体外循环下冠状动脉旁路移植术围术期脑损伤的比较研究. 中国循环杂志, 2003, 18(6):449-452.
20. Shaaban Ali M, Hamer M, Vaughan RS, et al. Early release pattern of S100 protein as q marker of brain damage after warm cardiopulmonary bypass. Anaesthesia, 2000, 55(8): 802-806.
21. Westaby S, Johnsson P, Parry AJ, et al. Serum S100 protein: a potential marker for cerebral events during cardiopulmonary bypass. Ann Thorac Surg. 1996, 61(1):88-92.
22. 高杨, 张兰, 谷兴华, 等. 连续检测血清 S100B 在体外循环心脏手术中的意义. 中华检验医学杂志, 2004, 27(4): 238-239.
1. Paparella D, Yau TM, Young E.Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. Eur J Cardiothorac Surg.2002,21(2):232-244
2. Redding GJ. Current concepts in adult respiratory distress syndrome in children. Curr Opin Pediatr, 2001,13(3):261-266.
3. 毛斌,周其文,韦华,来永强,张红.体外循环后的肺损伤及其炎症反应.中华胸心血管外科杂志 2000;16:225-227
4. Martin TR, Nakamura M, Matute-Bello G. The role of apoptosis in acute lung injury. Crit Care Med, 2003,31(4 Suppl):S184-188.
5. Ortiz LA, Moroz K, Liu JY, et al. Alveolar macrophage apoptosis and TNF-alpha, but not p53, expression correlate with murine response to bleomycin. Am J Physiol, 1998, 275(6 Pt1):L1208-1218.
6. Carney DE, Lutz CJ, Picone AL, et al. Soluble tumor necrosis factor receptor prevents post-pump syndrome.J Surg Res,1999,83(2):113-121.
7. 石践, 陆学东, 邵展社, 李学文等. 心脏直视手术中糖皮质激素对血浆细胞因子的影响. 中国现代医学杂志,2003, 13(15):10-12.
8. Kotani N, Hashimoto H, Sessler DI, et al. Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines. Anesth Analg, 2000,90(5):1039-1045.
9. 黄毅, 黄海波, 蓝鸿钧, 孙宗全. 体外循环术后血中细胞因子及其诱生能力变化的研究. 中华麻醉学杂志, 20(5):261-264.
10. Steinberg JB, Kapelanski DP, Olson JD, Weiler JM. Cytokine and complement levels in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg, 1993;106(6):1008-1016
11. Lin E, Calvano SE, Lowry SF. Inflammatory cytokines and cell response in surgery. Surgery. 2000, 127(2):117-126.
12. Finn A, Naik S, Klein N, et al. Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg, 1993,105(2):234-241.
13. Sekido N,Mukaida N,Harada A,et al.Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature, 1993, 365:654-657.
14. Kotani N, Hashimoto H, Sessler DI. Neutrophil number and interleukin-8 and elastase concentration in bronchoalveolar lavage fluid correlate with decreasedarterial oxygenation after cardiopulmonary bypass[J]. Anesth Analg. 2000, 90(5):1046-1051.
15. Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest, 1997,112(3):676-692.
16. Qing M,Vazquez-Jimenez JF,Klosterhalfen B,et al.Influence of temperature during cardiopulmonary bypass on leukocyte activation, cytokine balance,and post-operative organ damage[J].Shock 2001 May; 15(5):372-377
17. 曹新来, 胡小琴, 付亚琴.抑肽酶对体外循环心脏手术患者细胞因子的影响.临床麻醉杂志 2001,17(9):476-477.
18. Sugita T, Watarida S, Katsuyama K, et al. Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. J Cardiovasc Surg(Torino), 2002,43(4):437-440.
19. 舒强, 杨欣玮, 石卓, 施珊珊, 等. 乌司他丁对小儿体外循环术后肺损伤的保护作用. 中华急诊医学杂志, 2005,14(12):1027-1030.
20. Bronicki RA,Backer CL,Baden HP,et al.Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children[J].Ann Thorac Surg.2000,69(5):1490-1495.
21. Kotani N, Hashimoto H, Sessler DI, et al. Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines. Anesth Analg, 2000,90(5):1039-1045.
22. Lodge AJ, Chai PJ, Daggett CW, et al. Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets: timing of dose is important. [J]. J Thoracic Cardiovasc Surg, 1999, 117(3):515-522.
23. 于洋, 祁丹妮, 夏求明. 抗肿瘤坏死因子 α 抗体对体外循环肺损伤的保护作用. 中国胸心血管外科临床杂志, 2004,11(1)35-38.
24. 刘锦纷主译. 北京大学医学出版社 小儿心脏外科学. 2005,155-174.
2. 谢立刚, 胡小琴, 吴新民, 等. 心血管手术后早期神经精神并发症的调查. 中国循环杂志, 2001,16: 369-371.
3. Selnes OA, Goldsborough MA, Borowicz LM, et al. Neurobehavioural sequelae of cardiopulmonary bypass. Lancet, 1999, 353: 1601-1606.
4. Georgiadis D, Berger A, Kowatschev E, et al. Predictive value of S100βand neuron-specific enolase levels for adverse neurologic outcome after cardiac surgery. J Thorac Cardiovasc Surg. 2000, 119(1):138-147.
5. Mussack T, Biberthaler P, Kanz KG, et al. Immediate S-100B and neuron specific enolase plasma measurements for rapid evaluation of primary brain damage in alcohol-intoxicated, minor head-injured patients. Shock.. 2002, 18(5): 395-400.
6. Vingerhoets G, Van Nooten G, Vermassen F, et al. Short-term and long-term neuropsychological consequences of cardiac surgery with extracorporeal circulation. Eur J Cardiothorac Surg, 1997, 11(3): 424-431.
7. 吴万福, 胡长林. 炎性细胞因子在脑出血继发性脑损害中的作用. 国外医学脑血管疾病分册. 2005, 13(4):303-306.
8. 周建美, 邹定全, 常业恬. 体外循环心脏手术病人脑组织炎性细胞因子与脑损伤的关系. 中华麻醉学杂志, 2005, 25(12): 939-940.
9. 刘传绶, 董培青. 常温体外循环现状. 中华胸心血管外科杂志, 2000, 16(2): 116-118.
10. Morganti-Kossmann MC, Rancan M, Otto VI, et al. Role of cerebral inflammation after traumatic brain injury: a revisited concept. Shock, 2001, 16(3): 165-177.
11. Goto T, Baba T, Honma K, et al. Magnetic resonance imaging findings and postoperative neurologic dysfunction in elederly patients undergoing coronary artery bypass grafting. Ann Thorac Surg, 2001, 72(1):137-142.
12. Huang TL, Banion MK. Interleukin-1βand tumor necrosis factor-alpha suppress dexamethasone induction of glutamine synthetase in primary mouse astrocytes. J Neurochem, 1998,71(4): 1436-1442.
13. 高玲, 黄鹏, 潘慧, 祝世功. 促炎性细胞因子诱导 NF-κB 激活促进神经细胞凋亡机制. 中国病理生理杂志, 2005, 21(8):1648
14. Steinberg JB, Kapelanski DP, Olson JD, Weiler JM. Cytokine and complementlevels in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg, 1993;106(6):1008-1016.
15. LeMaire SA, Bhama JK, Schmittling ZC, et al. S100B correlates with neurologic complications after aortic operation using circulatory arrest. Ann Thorac Surg, 2001,71(6): 1913-1918.
16. Basile AM, Fusi C, Conti AA, et al. S100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study. Eur Neurol, 2001,45(3):151-159.
17. Ali MS, Harmer M, Vaughan R. Serum S100 protein as a maker of cerebral damage during cardiac surgery. British Journal of Anaesthesia, 2000, 85(2):287-298.
18. 程卫平, 杨九光. 体外循环围术期精神评价手段. 见: 龙村主编, 体外循环学. 北京, 人民军医出版社, 2004, 112
19. 高长青, 贺涛, 李伯君, 等. 非体外循环与体外循环下冠状动脉旁路移植术围术期脑损伤的比较研究. 中国循环杂志, 2003, 18(6):449-452.
20. Shaaban Ali M, Hamer M, Vaughan RS, et al. Early release pattern of S100 protein as q marker of brain damage after warm cardiopulmonary bypass. Anaesthesia, 2000, 55(8): 802-806.
21. Westaby S, Johnsson P, Parry AJ, et al. Serum S100 protein: a potential marker for cerebral events during cardiopulmonary bypass. Ann Thorac Surg. 1996, 61(1):88-92.
22. 高杨, 张兰, 谷兴华, 等. 连续检测血清 S100B 在体外循环心脏手术中的意义. 中华检验医学杂志, 2004, 27(4): 238-239.
1. Paparella D, Yau TM, Young E.Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. Eur J Cardiothorac Surg.2002,21(2):232-244
2. Redding GJ. Current concepts in adult respiratory distress syndrome in children. Curr Opin Pediatr, 2001,13(3):261-266.
3. 毛斌,周其文,韦华,来永强,张红.体外循环后的肺损伤及其炎症反应.中华胸心血管外科杂志 2000;16:225-227
4. Martin TR, Nakamura M, Matute-Bello G. The role of apoptosis in acute lung injury. Crit Care Med, 2003,31(4 Suppl):S184-188.
5. Ortiz LA, Moroz K, Liu JY, et al. Alveolar macrophage apoptosis and TNF-alpha, but not p53, expression correlate with murine response to bleomycin. Am J Physiol, 1998, 275(6 Pt1):L1208-1218.
6. Carney DE, Lutz CJ, Picone AL, et al. Soluble tumor necrosis factor receptor prevents post-pump syndrome.J Surg Res,1999,83(2):113-121.
7. 石践, 陆学东, 邵展社, 李学文等. 心脏直视手术中糖皮质激素对血浆细胞因子的影响. 中国现代医学杂志,2003, 13(15):10-12.
8. Kotani N, Hashimoto H, Sessler DI, et al. Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines. Anesth Analg, 2000,90(5):1039-1045.
9. 黄毅, 黄海波, 蓝鸿钧, 孙宗全. 体外循环术后血中细胞因子及其诱生能力变化的研究. 中华麻醉学杂志, 20(5):261-264.
10. Steinberg JB, Kapelanski DP, Olson JD, Weiler JM. Cytokine and complement levels in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg, 1993;106(6):1008-1016
11. Lin E, Calvano SE, Lowry SF. Inflammatory cytokines and cell response in surgery. Surgery. 2000, 127(2):117-126.
12. Finn A, Naik S, Klein N, et al. Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg, 1993,105(2):234-241.
13. Sekido N,Mukaida N,Harada A,et al.Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature, 1993, 365:654-657.
14. Kotani N, Hashimoto H, Sessler DI. Neutrophil number and interleukin-8 and elastase concentration in bronchoalveolar lavage fluid correlate with decreasedarterial oxygenation after cardiopulmonary bypass[J]. Anesth Analg. 2000, 90(5):1046-1051.
15. Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest, 1997,112(3):676-692.
16. Qing M,Vazquez-Jimenez JF,Klosterhalfen B,et al.Influence of temperature during cardiopulmonary bypass on leukocyte activation, cytokine balance,and post-operative organ damage[J].Shock 2001 May; 15(5):372-377
17. 曹新来, 胡小琴, 付亚琴.抑肽酶对体外循环心脏手术患者细胞因子的影响.临床麻醉杂志 2001,17(9):476-477.
18. Sugita T, Watarida S, Katsuyama K, et al. Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. J Cardiovasc Surg(Torino), 2002,43(4):437-440.
19. 舒强, 杨欣玮, 石卓, 施珊珊, 等. 乌司他丁对小儿体外循环术后肺损伤的保护作用. 中华急诊医学杂志, 2005,14(12):1027-1030.
20. Bronicki RA,Backer CL,Baden HP,et al.Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children[J].Ann Thorac Surg.2000,69(5):1490-1495.
21. Kotani N, Hashimoto H, Sessler DI, et al. Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines. Anesth Analg, 2000,90(5):1039-1045.
22. Lodge AJ, Chai PJ, Daggett CW, et al. Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets: timing of dose is important. [J]. J Thoracic Cardiovasc Surg, 1999, 117(3):515-522.
23. 于洋, 祁丹妮, 夏求明. 抗肿瘤坏死因子 α 抗体对体外循环肺损伤的保护作用. 中国胸心血管外科临床杂志, 2004,11(1)35-38.
24. 刘锦纷主译. 北京大学医学出版社 小儿心脏外科学. 2005,155-174.