空气肺复张对食管癌患者术中单肺通气诱导的肺组织氧化应激损伤的影响
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摘要
目的:观察术中需行单肺通气的食管癌患者肺复张诱导的肺组织氧化应激损伤以及空气肺复张的保护作用。
方法:选取32例ASAⅠ～Ⅱ级,择期行食管癌切除、胃食管吻合术的患者。按照手术当中实施单肺通气与否、单肺通气时间长短以及使用纯氧或空气膨肺,分为以下4组,每组8名患者:A组:术中不实施单肺通气,采用小潮气量通气和间断的手控呼吸。术毕关胸前使用纯氧膨肺。B组:单肺通气时间小于120min,术毕关胸前使用纯氧膨肺。C组:单肺通气时间大于120min,术毕关胸前使用纯氧膨肺。D组(治疗组)单肺通气时间大于120min,术毕关胸前使用空气膨肺。每组采用统一的术前用药、麻醉用药和检测手段。分别于T1:麻醉诱导成功后单肺通气前(A组为麻醉诱导后开胸前)、T2:单肺通气转为双肺通气前(A组为膨肺之前)、T3:单肺通气转为双肺通气后5min(A组为膨肺后5min)采取动脉血5ml迅速离心,取上层血浆于-70℃超低温冰箱保存,测定血中MDA、SOD、IL-6、IL-8、TNF-α以及蛋白羰基水平作为氧化应激指标。并在T1时间点与术后24h(T4)采动脉血做血气分析,检测PaO2、PaCO2并计算PaO2/FiO2以评估肺功能。
结果:蛋白羰基、SOD和MDA水平在A组各时间点无显著差异(p＞0.05),在B、C、D组T3时间点蛋白羰基和MDA水平显著增高、SOD水平显著降低,且变化程度C＞B＞D(p＜0.05):IL-6、IL-8和TNF-α水平在各组T2时间点显著增高,且C=D＞B＞A(p＜0.05)。术后24小时各组氧合指数显著降低,且变化程度C＞B＞D＞A(p＜0.05)。
结论:胸科手术术中单肺通气会导致氧化应激反应的发生,这一过程主要发生在肺复张的环节。氧化应激损伤的严重程度与单肺通气时间的长短有关,单侧肺萎陷时间越长的患者,肺复张后氧化应激损伤越严重。使用空气进行肺复张会减轻氧化应激损伤,具有肺保护作用。
Objectives :To observe the oxidative stress injury induced by lung expation during one-lung ventilation in esophageal cancer patients and the protective effect of air conducted lung expansion.
Methods:32 patients of esophageal cancer receiving selective surgery ASA grade I-II were divided into four groups , each group include 8 patients . Group A : To these patients , no one-lung ventilation was applied during surgery , and the lung expansion was conducted by pure oxygen . Group B : For these patients , one-lung ventilation applied during surgery was less than 120 minutes and the lung expansion was conducted by pure oxygen . Group C : For these patients , one-lung ventilation applied during surgery was more than 120 minutes and the lung expansion was conducted by pure oxygen . Group D (Treatment group) : For these patients , one-lung ventilation applied during surgery was more than 120 minutes and the lung expansion was conducted by air . Other methods of anaesthesia , medication and monitoring were all the same in each group . Blood samples were collected for each patient at : T1 - after one-lung ventilation was established; T2 - just before the lung expansion ; T3 - 5 minutes after the lung expansion . Those blood samples were collected for the measurement of MDA , SOD , IL-6 , IL-8 , TNF-αand plasma protein carbonyl levels as the indicators of oxidative stress injury. And a artery blood sample was taken to detect the oxygenation index 24 hours after the surgery as a indicator of lung function .
Results : The levels of plasma protein carbonyl and MDA were significantly higher in group B , C and D at T3 , and with the level of SOD significantly lower .The extent of variation C>B>D . (p<0.05) The levels of IL-6 , IL-8 , TNF-αwere significantly higher in all groups ,with the extent of variation C=D>B>A .(p<0.05) The oxygenation index was significantly lower in all groups ,with the extent of variation C>B>D>A .(p<0.05)
Conclusions : One-lung ventilation will cause oxidative stress injury, especially during lung expansion . Air conducted lung expansion will reduce the extent of oxidative stress injury and protect lung function .
方法:选取32例ASAⅠ～Ⅱ级,择期行食管癌切除、胃食管吻合术的患者。按照手术当中实施单肺通气与否、单肺通气时间长短以及使用纯氧或空气膨肺,分为以下4组,每组8名患者:A组:术中不实施单肺通气,采用小潮气量通气和间断的手控呼吸。术毕关胸前使用纯氧膨肺。B组:单肺通气时间小于120min,术毕关胸前使用纯氧膨肺。C组:单肺通气时间大于120min,术毕关胸前使用纯氧膨肺。D组(治疗组)单肺通气时间大于120min,术毕关胸前使用空气膨肺。每组采用统一的术前用药、麻醉用药和检测手段。分别于T1:麻醉诱导成功后单肺通气前(A组为麻醉诱导后开胸前)、T2:单肺通气转为双肺通气前(A组为膨肺之前)、T3:单肺通气转为双肺通气后5min(A组为膨肺后5min)采取动脉血5ml迅速离心,取上层血浆于-70℃超低温冰箱保存,测定血中MDA、SOD、IL-6、IL-8、TNF-α以及蛋白羰基水平作为氧化应激指标。并在T1时间点与术后24h(T4)采动脉血做血气分析,检测PaO2、PaCO2并计算PaO2/FiO2以评估肺功能。
结果:蛋白羰基、SOD和MDA水平在A组各时间点无显著差异(p＞0.05),在B、C、D组T3时间点蛋白羰基和MDA水平显著增高、SOD水平显著降低,且变化程度C＞B＞D(p＜0.05):IL-6、IL-8和TNF-α水平在各组T2时间点显著增高,且C=D＞B＞A(p＜0.05)。术后24小时各组氧合指数显著降低,且变化程度C＞B＞D＞A(p＜0.05)。
结论:胸科手术术中单肺通气会导致氧化应激反应的发生,这一过程主要发生在肺复张的环节。氧化应激损伤的严重程度与单肺通气时间的长短有关,单侧肺萎陷时间越长的患者,肺复张后氧化应激损伤越严重。使用空气进行肺复张会减轻氧化应激损伤,具有肺保护作用。
Objectives :To observe the oxidative stress injury induced by lung expation during one-lung ventilation in esophageal cancer patients and the protective effect of air conducted lung expansion.
Methods:32 patients of esophageal cancer receiving selective surgery ASA grade I-II were divided into four groups , each group include 8 patients . Group A : To these patients , no one-lung ventilation was applied during surgery , and the lung expansion was conducted by pure oxygen . Group B : For these patients , one-lung ventilation applied during surgery was less than 120 minutes and the lung expansion was conducted by pure oxygen . Group C : For these patients , one-lung ventilation applied during surgery was more than 120 minutes and the lung expansion was conducted by pure oxygen . Group D (Treatment group) : For these patients , one-lung ventilation applied during surgery was more than 120 minutes and the lung expansion was conducted by air . Other methods of anaesthesia , medication and monitoring were all the same in each group . Blood samples were collected for each patient at : T1 - after one-lung ventilation was established; T2 - just before the lung expansion ; T3 - 5 minutes after the lung expansion . Those blood samples were collected for the measurement of MDA , SOD , IL-6 , IL-8 , TNF-αand plasma protein carbonyl levels as the indicators of oxidative stress injury. And a artery blood sample was taken to detect the oxygenation index 24 hours after the surgery as a indicator of lung function .
Results : The levels of plasma protein carbonyl and MDA were significantly higher in group B , C and D at T3 , and with the level of SOD significantly lower .The extent of variation C>B>D . (p<0.05) The levels of IL-6 , IL-8 , TNF-αwere significantly higher in all groups ,with the extent of variation C=D>B>A .(p<0.05) The oxygenation index was significantly lower in all groups ,with the extent of variation C>B>D>A .(p<0.05)
Conclusions : One-lung ventilation will cause oxidative stress injury, especially during lung expansion . Air conducted lung expansion will reduce the extent of oxidative stress injury and protect lung function .
引文
1. Voiglio EJ,Coats TJ,Baudoin YP,et al.Resuscitative transverse thoracotomy[J].Ann Chir,2003,128(10):728-733.
2. Williams EA, Quinlan GJ, Goldstraw P, et al. Postoperative lung injury and oxidative damage in patients undergoing pulmonary resection. Eur Respir J 1998;11:1028-34.
3. Lases EC, Duurkens VA, GerritsenWB, et al. Oxidative stress after lung resection therapy: a pilot study. Chest 2000; 117:999-1003.
4. Moloney ED, Mumby SE, Gajdosci R, et al. Exhaled breath condensate detects markers of pulmonary inflammation after cardiothoracic surgery. Am J Respir Crit Care Med 2004; 169:64-69.
5. Misthos P, Katsaragakis S, Milingos N, et al. Postresectional pulmonary oxidative stress in lung cancer patients: the role of one-lung ventilation. Eur J Cardio-thoracic Surg 2005; 27:379-383.
6. Cheng, YJ, Chan, KC, Chi en, CT, et al Oxidative stress during 1-lung ventilation. J Thorac Cardiovasc Surg 2006; 132,513-518
7. Sylvester JT. Hypoxic pulmonary vasoconstriction: a radical view. Circ Res 2001;88:1259-66.
8. Paniker NV,Srivastava SK,Beutler E.Glutathuone metabolism of the red cells.Effect of glutathione reductase deficiency on the stimulation of hexose monophosphate shunt under oxidative stress.Biochim Biophys Acta, 1970, 215(3):456-460.
9. Grace P. Ischaemia-reperfusion injury. Br J Surg 1994;81:637-47.
10. Maus U,Rosseau S,Knies U,et al.Experssion of proinflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia.Eur Respir J 1998;11:534-41.
11. Wan S ,LeClerc JL, Vincent JL.Cytokine responses to cardiopulmonary bypass:lessons learned form cardiac transplantation.Ann Thorac Surg, 1997 Jun,63:269-76.
12.Abraham E,Carmody A,Shenkar R,et al.Neutrophils as early immunologic effector in hemorrhage or endotoxemia-induced acute lung injure[J].Am J Physiol lung Cell Mol Physiol,2000,279:1137-1145.
13.Song Y,Ao I,Calkins CM,et al.Differential cardiopulmonary recruitment of neutrophils during hemorrhagic shock:a role forICAM-1?[J].Shock,2001,16(6):444-8
14.崔社怀,郭先键,钱桂生.肺表面张力与肿瘤坏死因子在急性低氧油酸性肺损伤时的变化[J].中国危重病急救医学,2000,12(1):3-6.
15.Xie GQ,Jiang JX,Chen Y H,et al.Induction of acute hepatic injure by endotoxin in mice[J].Hepatobiilary Pancreat DisInt,2002,1940:558-564
16.Kim GY,Rob SL,Park SK,et al.Alleviation of experimental septic shock in mice by acidic polysaccharide isolated from the medicinal mushroom phellinus linteus[J].Biol Pharm Bull,20 03,26(10):1418-1423
17.Schutte H,Lohmeyer J,RossesuS,et al.Bornchoalveolar and systemic cytokine profiles in patients with ARDS,severe pneumonia and cardiogemc pulmonary oedems.EurR espirJ 1996;9:1858-67.
18.Boutten A,Dehaur MS,Seta N et al.Compartmentalized IL-8 and elastase release within the human lung in unilateral pneumoma Am J Respir Crit Care Med 1996;153:336-42
1.Voiglio EJ,Coats TJ,Baudoin YP,et al.Resuscitative transverse thoracotomy[J].Ann Chir,2003,128(10):728-733.
2.Bernard GR,Artigas A,Brigham KL,et al.The American-European Consensus on ARDS.Am J Respir Crit Care Med 1994;149:818-824.
3.Kutlu CA,Williams EA,Evans TW,et al.Acute lung injury and acute respiratory distress syndrome after pulmonary resection.Ann Thorac Surg 2000;69:376-380
4.Ruffini E,Paola A,Papalia E,et al.Frequency and mortality of acute lung injury and acute respiratory distress syndrome after pulmonary resection for bronchogenic carcinoma.Eur J Cardiothorac Surg 2001;20:30-37.
5.Licker M,de Perrot M,Spiliopoulos A,et al.Risk factors for acute lung injury after thoracic surgery for lung cancer.Anesth Analg 2003;97:1558-1565.
6.Paniker NV,Srivastava SK,Beutler E.Glutathuone metabolism of the red cells.Effect of glutathione reductase deficiency on the stimulation of hexose monophosphate shunt under oxidative stress.Biochim Biophys Acta,1970,215(3):456-460.
7.Fukanoshi T,Ishibe Y,Okazaki N,Miura K,Liu R,Nagai S,Minami Y.Effect of re-expansion after short-period lung collapse on pulmonary capillary permeability and pro-inflammatory cytokine gene expression in isolated rabbit lungs.Br J Anaesth 2004;92:558-63.
8.Williams EA,Quinlan GJ,Goldstraw P,et al.Postoperative lung injury and oxidative damage in patients undergoing pulmonary resection. Eur Respir J 1998;11:1028-34.
9. Lases EC, Duurkens VA, GerritsenWB, et al. Oxidative stress after lung resection therapy: a pilot study. Chest 2000;117:999-1003.
10. Moloney ED, Mumby SE, Gajdosci R, et al. Exhaled breath condensate detects markers of pulmonary inflammation after cardiothoracic surgery. Am J Respir Crit Care Med 2004; 169:64-69.
11. Grace P. Ischaemia-reperfusion injury. Br J Surg 1994;81:637-47.
12. Perrot de M, Liu M, Waddell TK, Keshayjee S. Ischemia-reperfusioninduced lung injury. Am J Respir Crit Care Med 2003; 167:490-511.
13. Chow CW, Abreu MTH, Suzuki T, Downey GP. Oxidative stress and acute lung injury. Am J Respir Cell Mol Biol 2003;29:427-31.
14. Sylvester JT. Hypoxic pulmonary vasoconstriction: a radical view. Circ Res 2001;88:1259-66.
15. Li C, Jackson RM. Reactive species mechanisms of cellular hypoxiareoxygenation injury. Am J Physiol Cell Physiol 2002;282:C227-C41.
16. Lang JD, McArdle J, O'Reilly PJ, Matalon S. Oxidant-antioxidant balance in acute lung injury. Chest 2002;122: 314S-320S.
17. Comhair SAA, Erzurum SC. Antioxidant responses to oxidant-mediated lung diseases. Am J Physiol Lung Cell Mol Physiol 2002;283:L246-55.
18. Misthos P, Katsaragakis S, Milingos N, et al. Postresectional pulmonary oxidative stress in lung cancer patients: the role of one-lung ventilation. Eur J Cardio-thoracic Surg 2005; 27:379-383.
19. Misthos P, Katsaragakis S, Theodorou D, Milingos N, Skottis I. The degree of oxidative stress is associated with major adverse effects after lung resection: a prospective study. Eur J Cardiothorac Surg 2006;29:591—5.
20. Cheng, YJ, Chan, KC, Chien, CT, et al Oxidative stress during 1-lung ventilation.J Thorac Cardiovasc Surg 2006;132,513-518
21. Grichnik KP, D'Amico TA. Acute lung injury and acute respiratory distress syndrome after pulmonary resection. Semin Cardiothorac Vasc Anesth 2004;8:317-34.
22.谭正怀 刘耕陶.氧化应激与急性肺损伤[J].国外医学:呼吸系统分册,2005,25:39-44.
23.Fakhrzadeh L,Laskin JD,Laskin DL.Deficiency in inducible nitric oxide synthase protects mice from ozone-induced lung inflammation and tissue injury.Am J Respir Cell Mol Biol,2002,26(4):413-419.
24.Radomski A,Sawicki G,Olson DM,et al.The role of nitric oxide and metalloproteinases in the pathogenesis of hyperoxia-induced lung injury in new born rats.Br J Pharmacol,1998,125(7):1455-1462.
25.Laskin DL,Fakhrzadeh L,Laskin JD.Nitric oxide and peroxynitrite in ozone-induced lung injury.Adv Exp Med Biol,2001,500(2):183-190.
26.Lu MY,Kang BH,Wan FJ,et al.Hyperbaric oxygen attenuates lipopolysaccharide induced acute lung injury.Intensive Care Med,2002,28(5):636-641.
27.Nagata K,Iwasaki Y,Takemura Y,et al.Effect of inhaled NG-nitro-L-arginine methyl ester on Candida-induced acute lung injury.Chest,2003,124(6):2293-2301.
28.Shanley TP,Zhao B,Macariola DR,et al.Role of nitric oxide in acute lung inflammation:lessons learned from the inducible nitric oxide synthase knockout mouse.Crit Care Med,2002,30(9):1960-1968.
29.Ginzberg HH,Cherapanov V,Dong Q,Cantin A,McCulloch CA,Shannon PT,and Downey GP.Neutrophil-mediated epithelial injury during transmigration:role of elastase.Am J Physiol Gastrointest Liver Physiol 281:G705-G717,2001
30.Feldhaus,M.J.,et al.2002.Ceramide generation in situ alters leukocyte cytoskeletal organization and beta 2-integrin function and causes complete degranulation.J.Biol.Chem.277:4285-4293.
31.Yoshida,N.,et al.1999.Vitamin E protects against polymorphonuclear leukocyte-dependent adhesion to endothelial cells.J.Leukoc.Biol.65:757-763.
2. Williams EA, Quinlan GJ, Goldstraw P, et al. Postoperative lung injury and oxidative damage in patients undergoing pulmonary resection. Eur Respir J 1998;11:1028-34.
3. Lases EC, Duurkens VA, GerritsenWB, et al. Oxidative stress after lung resection therapy: a pilot study. Chest 2000; 117:999-1003.
4. Moloney ED, Mumby SE, Gajdosci R, et al. Exhaled breath condensate detects markers of pulmonary inflammation after cardiothoracic surgery. Am J Respir Crit Care Med 2004; 169:64-69.
5. Misthos P, Katsaragakis S, Milingos N, et al. Postresectional pulmonary oxidative stress in lung cancer patients: the role of one-lung ventilation. Eur J Cardio-thoracic Surg 2005; 27:379-383.
6. Cheng, YJ, Chan, KC, Chi en, CT, et al Oxidative stress during 1-lung ventilation. J Thorac Cardiovasc Surg 2006; 132,513-518
7. Sylvester JT. Hypoxic pulmonary vasoconstriction: a radical view. Circ Res 2001;88:1259-66.
8. Paniker NV,Srivastava SK,Beutler E.Glutathuone metabolism of the red cells.Effect of glutathione reductase deficiency on the stimulation of hexose monophosphate shunt under oxidative stress.Biochim Biophys Acta, 1970, 215(3):456-460.
9. Grace P. Ischaemia-reperfusion injury. Br J Surg 1994;81:637-47.
10. Maus U,Rosseau S,Knies U,et al.Experssion of proinflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia.Eur Respir J 1998;11:534-41.
11. Wan S ,LeClerc JL, Vincent JL.Cytokine responses to cardiopulmonary bypass:lessons learned form cardiac transplantation.Ann Thorac Surg, 1997 Jun,63:269-76.
12.Abraham E,Carmody A,Shenkar R,et al.Neutrophils as early immunologic effector in hemorrhage or endotoxemia-induced acute lung injure[J].Am J Physiol lung Cell Mol Physiol,2000,279:1137-1145.
13.Song Y,Ao I,Calkins CM,et al.Differential cardiopulmonary recruitment of neutrophils during hemorrhagic shock:a role forICAM-1?[J].Shock,2001,16(6):444-8
14.崔社怀,郭先键,钱桂生.肺表面张力与肿瘤坏死因子在急性低氧油酸性肺损伤时的变化[J].中国危重病急救医学,2000,12(1):3-6.
15.Xie GQ,Jiang JX,Chen Y H,et al.Induction of acute hepatic injure by endotoxin in mice[J].Hepatobiilary Pancreat DisInt,2002,1940:558-564
16.Kim GY,Rob SL,Park SK,et al.Alleviation of experimental septic shock in mice by acidic polysaccharide isolated from the medicinal mushroom phellinus linteus[J].Biol Pharm Bull,20 03,26(10):1418-1423
17.Schutte H,Lohmeyer J,RossesuS,et al.Bornchoalveolar and systemic cytokine profiles in patients with ARDS,severe pneumonia and cardiogemc pulmonary oedems.EurR espirJ 1996;9:1858-67.
18.Boutten A,Dehaur MS,Seta N et al.Compartmentalized IL-8 and elastase release within the human lung in unilateral pneumoma Am J Respir Crit Care Med 1996;153:336-42
1.Voiglio EJ,Coats TJ,Baudoin YP,et al.Resuscitative transverse thoracotomy[J].Ann Chir,2003,128(10):728-733.
2.Bernard GR,Artigas A,Brigham KL,et al.The American-European Consensus on ARDS.Am J Respir Crit Care Med 1994;149:818-824.
3.Kutlu CA,Williams EA,Evans TW,et al.Acute lung injury and acute respiratory distress syndrome after pulmonary resection.Ann Thorac Surg 2000;69:376-380
4.Ruffini E,Paola A,Papalia E,et al.Frequency and mortality of acute lung injury and acute respiratory distress syndrome after pulmonary resection for bronchogenic carcinoma.Eur J Cardiothorac Surg 2001;20:30-37.
5.Licker M,de Perrot M,Spiliopoulos A,et al.Risk factors for acute lung injury after thoracic surgery for lung cancer.Anesth Analg 2003;97:1558-1565.
6.Paniker NV,Srivastava SK,Beutler E.Glutathuone metabolism of the red cells.Effect of glutathione reductase deficiency on the stimulation of hexose monophosphate shunt under oxidative stress.Biochim Biophys Acta,1970,215(3):456-460.
7.Fukanoshi T,Ishibe Y,Okazaki N,Miura K,Liu R,Nagai S,Minami Y.Effect of re-expansion after short-period lung collapse on pulmonary capillary permeability and pro-inflammatory cytokine gene expression in isolated rabbit lungs.Br J Anaesth 2004;92:558-63.
8.Williams EA,Quinlan GJ,Goldstraw P,et al.Postoperative lung injury and oxidative damage in patients undergoing pulmonary resection. Eur Respir J 1998;11:1028-34.
9. Lases EC, Duurkens VA, GerritsenWB, et al. Oxidative stress after lung resection therapy: a pilot study. Chest 2000;117:999-1003.
10. Moloney ED, Mumby SE, Gajdosci R, et al. Exhaled breath condensate detects markers of pulmonary inflammation after cardiothoracic surgery. Am J Respir Crit Care Med 2004; 169:64-69.
11. Grace P. Ischaemia-reperfusion injury. Br J Surg 1994;81:637-47.
12. Perrot de M, Liu M, Waddell TK, Keshayjee S. Ischemia-reperfusioninduced lung injury. Am J Respir Crit Care Med 2003; 167:490-511.
13. Chow CW, Abreu MTH, Suzuki T, Downey GP. Oxidative stress and acute lung injury. Am J Respir Cell Mol Biol 2003;29:427-31.
14. Sylvester JT. Hypoxic pulmonary vasoconstriction: a radical view. Circ Res 2001;88:1259-66.
15. Li C, Jackson RM. Reactive species mechanisms of cellular hypoxiareoxygenation injury. Am J Physiol Cell Physiol 2002;282:C227-C41.
16. Lang JD, McArdle J, O'Reilly PJ, Matalon S. Oxidant-antioxidant balance in acute lung injury. Chest 2002;122: 314S-320S.
17. Comhair SAA, Erzurum SC. Antioxidant responses to oxidant-mediated lung diseases. Am J Physiol Lung Cell Mol Physiol 2002;283:L246-55.
18. Misthos P, Katsaragakis S, Milingos N, et al. Postresectional pulmonary oxidative stress in lung cancer patients: the role of one-lung ventilation. Eur J Cardio-thoracic Surg 2005; 27:379-383.
19. Misthos P, Katsaragakis S, Theodorou D, Milingos N, Skottis I. The degree of oxidative stress is associated with major adverse effects after lung resection: a prospective study. Eur J Cardiothorac Surg 2006;29:591—5.
20. Cheng, YJ, Chan, KC, Chien, CT, et al Oxidative stress during 1-lung ventilation.J Thorac Cardiovasc Surg 2006;132,513-518
21. Grichnik KP, D'Amico TA. Acute lung injury and acute respiratory distress syndrome after pulmonary resection. Semin Cardiothorac Vasc Anesth 2004;8:317-34.
22.谭正怀 刘耕陶.氧化应激与急性肺损伤[J].国外医学:呼吸系统分册,2005,25:39-44.
23.Fakhrzadeh L,Laskin JD,Laskin DL.Deficiency in inducible nitric oxide synthase protects mice from ozone-induced lung inflammation and tissue injury.Am J Respir Cell Mol Biol,2002,26(4):413-419.
24.Radomski A,Sawicki G,Olson DM,et al.The role of nitric oxide and metalloproteinases in the pathogenesis of hyperoxia-induced lung injury in new born rats.Br J Pharmacol,1998,125(7):1455-1462.
25.Laskin DL,Fakhrzadeh L,Laskin JD.Nitric oxide and peroxynitrite in ozone-induced lung injury.Adv Exp Med Biol,2001,500(2):183-190.
26.Lu MY,Kang BH,Wan FJ,et al.Hyperbaric oxygen attenuates lipopolysaccharide induced acute lung injury.Intensive Care Med,2002,28(5):636-641.
27.Nagata K,Iwasaki Y,Takemura Y,et al.Effect of inhaled NG-nitro-L-arginine methyl ester on Candida-induced acute lung injury.Chest,2003,124(6):2293-2301.
28.Shanley TP,Zhao B,Macariola DR,et al.Role of nitric oxide in acute lung inflammation:lessons learned from the inducible nitric oxide synthase knockout mouse.Crit Care Med,2002,30(9):1960-1968.
29.Ginzberg HH,Cherapanov V,Dong Q,Cantin A,McCulloch CA,Shannon PT,and Downey GP.Neutrophil-mediated epithelial injury during transmigration:role of elastase.Am J Physiol Gastrointest Liver Physiol 281:G705-G717,2001
30.Feldhaus,M.J.,et al.2002.Ceramide generation in situ alters leukocyte cytoskeletal organization and beta 2-integrin function and causes complete degranulation.J.Biol.Chem.277:4285-4293.
31.Yoshida,N.,et al.1999.Vitamin E protects against polymorphonuclear leukocyte-dependent adhesion to endothelial cells.J.Leukoc.Biol.65:757-763.