不同潮气量对大鼠肺IL-6和STAT3表达及肺损伤的影响
|
摘要
目的:机械通气损伤机制复杂,是由多种炎症因子和炎症通路参与的炎症反应。而参与了众多肺部疾病的IL-6激活的STAT3通路是否参与了机械通气损伤以及其与机械通气损伤的关系目前还未见报导,因此本研究预探讨SD大鼠不同潮气量机械通气后肺损伤程度,肺组织中IL-6和STAT3表达水平,及其表达水平与机械通气肺损伤的关系。
方法:将2 4只健康雄性SD大鼠随机分成A组(对照组,假手术自主呼吸组)、B组(小潮气量通气组,10ml组)、C组(中等潮气量通气组,20ml组)、D组(大潮气量通气组,40ml组),每组6只。四组均接受麻醉后气管切开,A组自主呼吸2小时,B、C、D3组分别以不同潮气量机械通气2小时,吸入氧浓度为1.0,通气结束后拔管缝合单笼饲养恢复24小时。观察通气后24小时大鼠肺湿干重比(W/D),肺泡灌洗液(BALF)中白细胞(WBC)计数,光镜下肺组织病理学改变及肺损伤评分,免疫组化法测定肺组织中IL-6、STAT3蛋白的表达。
结果:
1.与无肺损伤的对照组A组比较,小潮气量10ml组B组W/D值、BALF中WBC计数和病理学评分均处于较低水平(P＞0.05),无明显肺损伤;20ml组C组和40ml组D组则W/D值、BALF中WBC计数和病理学评分处于较高水平(P＜0.01),肺损伤明显;D组指标明显高于C组(P＜0.05),肺损伤严重;
2.肺组织IL-6及STAT3表达水平:与A组比较,B组无统计学差异(P＞0.05),C组和D组则明显增高(P＜0.01),且D组高于C组(P＜0.05)。各组之间IL-6与STAT3呈正相关。
结论:
1.本研究结果提示大潮气量机械通气可促进肺部炎症反应的发生、发展,导致明显的肺损伤,小潮气量通气则限制肺组织局部的炎症反应,是肺保护性机械通气措施之一;
2.IL-6激活的STAT3通路可能参与了机械通气肺损伤过程。
Objective:The mechanism of ventilator-induced lung injury(VILI) is complicated,Which is inflammation participated by many inflammatory factors and pathways.The inflammatory pathway that Interleukin -6(IL-6)activated signal transducers and activators of transcription-3(STAT3)plays an important role in many lung diseases, but whether it participates the process of VILI remains unknown.Our study produces lung injury by mechanical ventilation,to explore the effects of different tidal volume on lung injury and the expression of lung IL-6 and STAT3 in the rats,and the relationship between the lung injury and the expression of lung IL-6 and STAT3.
Methods:24 Sprague-Dawley rats were randomly divided into 4 groups:A group(control),B group(10ml/kg ventilated),C group (20ml/kg ventilated),D group(40ml/kg ventilated).The rats accepted tracheotomy after anesthesia,A group kept breathing for 2 hour,B,C and D groups accepted ventilation for 2 hour,the inhalation of oxygen concentration was 1.0,recording vital sign of rats and doing blood gas analysis.The rats recovered 24 hour after ventilated,the lung wet/dry ratio,WBC counts in bronchoalveolar lavage fluid(BALF),lung tissue morphological change,the expression of lung IL-6 and STAT3 were tested.
Result:
1.Compared with A group,B group had no significant difference in wet/dry ratio,WBC counts in BALF,and the lung morphological change(P＞0.05).C group and D group had obviously lung injury,the wet/dry ratio,WBC counts in BALF,lung morphological change were higher or more serious than A and B group(P＜0.05),D group was serious than C group(P＜0.05).
2.The expression of IL-6 and STAT3 had no difference between A and B group(P＞0.05),C group and D group were higher than A and B group (P＜0.05),and D group was higher than C group(P＜0.05).The IL-6 and STAT3 was direct correlation among 4 groups.
Conclusions:
1.The high tidal volume mechanical ventilation can induce lung inflammation and injury,while reduced tidal volume diminished lung injury and inflammation,which is one of protecting lung ventilation method.
2.The inflammatory pathway that IL-6 activated STAT3 participates the process of VILI.
方法:将2 4只健康雄性SD大鼠随机分成A组(对照组,假手术自主呼吸组)、B组(小潮气量通气组,10ml组)、C组(中等潮气量通气组,20ml组)、D组(大潮气量通气组,40ml组),每组6只。四组均接受麻醉后气管切开,A组自主呼吸2小时,B、C、D3组分别以不同潮气量机械通气2小时,吸入氧浓度为1.0,通气结束后拔管缝合单笼饲养恢复24小时。观察通气后24小时大鼠肺湿干重比(W/D),肺泡灌洗液(BALF)中白细胞(WBC)计数,光镜下肺组织病理学改变及肺损伤评分,免疫组化法测定肺组织中IL-6、STAT3蛋白的表达。
结果:
1.与无肺损伤的对照组A组比较,小潮气量10ml组B组W/D值、BALF中WBC计数和病理学评分均处于较低水平(P＞0.05),无明显肺损伤;20ml组C组和40ml组D组则W/D值、BALF中WBC计数和病理学评分处于较高水平(P＜0.01),肺损伤明显;D组指标明显高于C组(P＜0.05),肺损伤严重;
2.肺组织IL-6及STAT3表达水平:与A组比较,B组无统计学差异(P＞0.05),C组和D组则明显增高(P＜0.01),且D组高于C组(P＜0.05)。各组之间IL-6与STAT3呈正相关。
结论:
1.本研究结果提示大潮气量机械通气可促进肺部炎症反应的发生、发展,导致明显的肺损伤,小潮气量通气则限制肺组织局部的炎症反应,是肺保护性机械通气措施之一;
2.IL-6激活的STAT3通路可能参与了机械通气肺损伤过程。
Objective:The mechanism of ventilator-induced lung injury(VILI) is complicated,Which is inflammation participated by many inflammatory factors and pathways.The inflammatory pathway that Interleukin -6(IL-6)activated signal transducers and activators of transcription-3(STAT3)plays an important role in many lung diseases, but whether it participates the process of VILI remains unknown.Our study produces lung injury by mechanical ventilation,to explore the effects of different tidal volume on lung injury and the expression of lung IL-6 and STAT3 in the rats,and the relationship between the lung injury and the expression of lung IL-6 and STAT3.
Methods:24 Sprague-Dawley rats were randomly divided into 4 groups:A group(control),B group(10ml/kg ventilated),C group (20ml/kg ventilated),D group(40ml/kg ventilated).The rats accepted tracheotomy after anesthesia,A group kept breathing for 2 hour,B,C and D groups accepted ventilation for 2 hour,the inhalation of oxygen concentration was 1.0,recording vital sign of rats and doing blood gas analysis.The rats recovered 24 hour after ventilated,the lung wet/dry ratio,WBC counts in bronchoalveolar lavage fluid(BALF),lung tissue morphological change,the expression of lung IL-6 and STAT3 were tested.
Result:
1.Compared with A group,B group had no significant difference in wet/dry ratio,WBC counts in BALF,and the lung morphological change(P＞0.05).C group and D group had obviously lung injury,the wet/dry ratio,WBC counts in BALF,lung morphological change were higher or more serious than A and B group(P＜0.05),D group was serious than C group(P＜0.05).
2.The expression of IL-6 and STAT3 had no difference between A and B group(P＞0.05),C group and D group were higher than A and B group (P＜0.05),and D group was higher than C group(P＜0.05).The IL-6 and STAT3 was direct correlation among 4 groups.
Conclusions:
1.The high tidal volume mechanical ventilation can induce lung inflammation and injury,while reduced tidal volume diminished lung injury and inflammation,which is one of protecting lung ventilation method.
2.The inflammatory pathway that IL-6 activated STAT3 participates the process of VILI.
引文
1 Hoegl S,Boost KA,Flondor M,et al.Short-term exposure to highpressureventilation leads to pulmonary biotranma and systemic inflammation in the rat.Int J Mol Med.2008 Apr;21(4):513-9.
2 Imanaka H,Shimaoka M,Matsuura N,et al.Ventilator-induced lung injury is associated with neutrophil infiltration,macrophage activation,and TGF-beta 1mRNA upregulation in rat lungs.Anesth Analg 2001;92:428-436.
3 Yamamoto H,Termoto H,Uetani K,et al.Stretch induces a growth factor in alveolar cells via protein kinase[J].Respire Physiol,2001,127(2-3):105.
4 Tremblay L N,Slutsky A S.Ventilator-induced injury:from Barotraumas to biotrauma[J].Proc Assoc Am Physcians,1998,110(6):482-488.
5 Nonas S,Birukova AA,Fu P,et al.Oxidized phospbolipids reduce ventilator-induced vascular leak and inflammation in vivo.Crit Care.2008 Jan 24;12(1):R27.
6 Ricard JD,Dreyfuss D,Sanmon G.Ventilator-induced lung injury.Curt Opin Crit Care.2002 Feb;8(1):12-20.
7 The Acute Respiratory Distress Syndrome Network.Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med 2000;342:1301-1308.
8 Melanie J.Scott,Christopher J.Godshall,and William G.Jaks,STATs,Cytokines,and Sepsis.Clinical and Diagnostic Laboratory Immunology,November 2002,p.1153-1159.
9 弓清梅,李建强,刘卓拉.大鼠急性肺损伤过程中STAT3的活化对bcl-2 bax 表达及细胞凋亡的影响.中国药物与临床,2007年1月第7卷第1期:35-37.
10 Nin N,Lorente JA,de Paula M,et al.Rats surviving injurious mechanical ventilation show reversible pulmonary,vascular and inflammatory changes.Intensive Care Med.2008 Jan 5.
11 Rodrigues SF,de Oliveira MA,Martins JO,et al.Differential effects of chloral hydrate- and ketamine/xylazine-induced anesthesia by the s.c.route.Life Sci, 2006,79:1630-7.
12 Hu GD,Cai SX,Chen B,Chen YH.Effects of serum of the rats ventilated with high tidal volume on endothelial cell permeability and therapeutic effects of ulinastatin.Chin Med J(Engl).2006 Aug 20;119(16):1374-80.
13 Kacmarek RM.Ventilator-associated lung injury.Int Anesthesiol Clin.1999,37(3):47-64.
14 Stuber F,Wrigge H,et al.Kinetic and reversibility of mechanical ventilator-associated pulmonary and systemic inflammatory response in patients with acute lung injury[J].Inten Care Med,2002,28:834-841.
15 陈惠香.机械通气对肺组织和全身炎症反应的影响[D].浙江大学,2003.
16 Kawano T,Moil S,Cybulsky M,et al.Effect of granulocyte Depletion in a ventilated surfactant-depleted lung.J Appl Physiol.1987,62:27-33.
17 唐柚青,郭振辉,邓青南,等.小潮气量通气对机械通气导致肺损伤及多器官功能衰竭中核因子-κB活性的影响.实用医学杂志,2007年第23卷第12期:1809-11.
18 冯丹,姚尚龙,尚游,等.大鼠机械通气所致肺损伤时p 38丝裂原活化蛋白激酶通路的激活.中国危重病急救医学,2007年2月第19卷第2期:77-80.
19 Kaynar AM,Houghton AM,Lum EH,et al.Neutrophil Elastase Is Needed for Neutrophil Emigration into Lungs in Ventilator-Induced Lung Injury.Am J Respir Cell Mol Biol.2008 Feb 14.
20 Sakashita A,Nishimura Y,Nishiuma T,et al.Neutrophil elastase inhibitor (sivelestat)attenuates subsequent ventilator-induced lung injury in mice.Eur J Pharmacol.2007 Sep 24;571(1):62-71.
21 Chemoff AE,Granowitz EV Shapiro L,et al.A randomized,controlled trial of IL-10 in humans.Inhibition of inflammatory cytokine production and immune responses.J Immunol.1995,154(10):5492-9.
22 Simons Rk,Junger WG Loomis WH,et al.Acute lung injury in Endotoxemic rats is associated with sustained circulating IL-6 levels and intrapulmonary CINC activity and neutrophil recruiment-role of circulating TNF-alpha and IL-beta?hock.1996,6:39-45.
23 Fujitani Y, Hibi M, Fukada T, et al. An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT. Oncogene. 1997 Feb 20;14(7):751-61.
24 Ihle JN. The STAT family in cytokine signaling. Curr Opin Cell Boil, 2001, 13(2): 211- 217.
25 Danell JE Jr. STATs and gene regulation. Science, 1997,277 (12): 1630.
26 Scott MJ, Godshall CJ, Cheadle WG. Jaks, STATs, Cytokines, and Sepsis. Clin Diagn Lab Immunol. 2002 Nov;9(6):1153-9.
27 Zhang X, Blenis J, Li HC et al. Requirement of serine phosphorylation for formation of STAT-promoter complexes. Science. 1995 Mar 31;267(5206): 1990-4.
28 Quinton LJ, Jones MR, Robson BE, et al. Alveolar Epithelial STAT3, IL-6 Family Cytokines, and Host Defense During Escherichia coli Pneumonia. Am J Respir Cell Mol Biol. 2008 Jan 10.
29 Wang G, Qian P, Jackson FR,et al.Sequential activation of JAKs, STATs and xanthine dehydrogenase/oxidase by hypoxia in lung microvascular endothelial cells. Int J Biochem Cell Biol. 2008;40(3):461-70.
30 Matsuzaki Y, Xu Y, Ikegami M,et al. Stat3 is required for cytoprotection of the respiratory epithelium during adenoviral infection. J Immunol. 2006 Jul 1;177(1):527-37.
31 Xu Y, Ikegami M, Wang Y,et al. Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells. BMC Genomics. 2007 Dec 10;8:455.
32 Vaneker M, Halbertsma FJ, van Egmond J, et al. Mechanical ventilation in healthy mice induces reversible pulmonary and systemic cytokine elevation with preserved alveolar integrity: an in vivo model using clinical relevant ventilation settings. Anesthesiology. 2007 Sep;107(3):419-26.
33 Halter JM, Steinberg JM, Gatto LA,et al. Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability. Crit Care. 2007; 11(1):R20.
34 Amato MB,Barbas CS,Medeiros DM,et al.Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome..N Engl J Med.1998 Feb 5;338(6):347-54.
35 Hierholzer C,Kalff JC,Omert L,et al.Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury.Am J Physiol.1998 Sep;275(3 Pt 1):L611-21.
36 Severgnini M,Takahashi S,Rozo LM,et al.Activation of the STAT pathway in acute lung injury.Am J Physiol Lung Cell Mol Physiol.2004 Jun;286(6):L1282-92.
1 Tremblay LN,Slutsky AS.Ventilator-induced injury:from Barotratuma to biotrauma.Proc Assoc Am Physicians,1998,110:482-488.
2 Kawano T,Mori S,Cybulsky M,et al.Effect of granulocyte Depletion in a ventilated surfactant-depleted lung.J Appl Physiol.1987,62:27-33.
3 Zhang H,Grasso S,Downey G et al.Mechanical ventilation Activates polymorphonuclear(PMN)cells.Am J Respir Crit Care Med,2 000,161:1095-1100.
4 张新日,杜永成,姜宏英,等。肺泡巨噬细胞活化在大鼠呼吸相关肺损伤中的作用。中华结核和呼吸杂志,2006年7月第29卷第7期:482-484.
5 Pugin J,Verghese G,Widmer MC,et al.The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome.Crit Care Med,1999,27:304-312.
6 Yamamoto H,Teramoto H,Uetani K,et al.Cyclic stretch up-regulates intefleukin-8 and transforming growth factor-betal production through a protein kinase C-dependent pathway in alveolar epithelial cells.Respirology.2002 Jun;7(2):103-9.
7 von Bethmann AN,Brasch F,Nusing R,et al.Hyperventilation induces release of cytokines from perfused mouse lung.Am J Respir Crit Care Med.1998 Jan;157(1):263-72.
8 Fingar VH,Buschemeyer WC,Johnston MN,et al.Constiutive and stimulated expression of ICAM-1 protein on pulmonary endothelian cells in vivo.Microvas Res,1997,54:135-146.
9 唐柚青,郭振辉,邓青南,等.小潮气量通气对机械通气导致肺损伤及多器官功能衰竭中核因子-κB活性的影响.实用医学杂志,2007年第23卷第12期:1809-11.
10 冯丹,姚尚龙,尚游,等.大鼠机械通气所致肺损伤时p 38丝裂原活化蛋白激酶通路的激活.中国危重病急救医学,2007年2月第19卷第2期:77-80.
11 Kaynar AM,Houghton AM,Lum EH,et al.Neutrophil Elastase Is Needed for Neutrophil Emigration into Lungs in Ventilator-Induced Lung Injury.Am J Respir Cell Mol Biol.2008 Feb 14.
12 Sakashita A,Nishimura Y,Nishiuma T,et al.Neutrophil elastase inhibitor (sivelestat)attenuates subsequent ventilator-induced lung injury in mice.Eur J Pharmacol.2007 Sep 24;571(1):62-71.
13 Chernoff AE,Granowitz EV Shapiro L,et al.A randomized,controlled trial of IL-10 in humans.Inhibition of inflammatory cytokine production and immune responses.J Immunol.1995,154(10):5492-9.
14 胡国栋,蔡绍曦,陈英华,等.不同潮气量机械通气对大鼠支气管和肺组织细胞凋亡的影响.第一军医大学学报.2005;25(5):508-12.
15 Syrkina O,Jafari B,Hales CA,et al.Oxidant stress mediates inflammation and apoptosis in ventilator-induced lung injury.Respirology.2008 May;13(3):333-40.
16 Hickling KG,Walsh J,Henderson S,et al.Low mortality rate in adult respiratory distress syndrome using low-volume,pressure-limited ventilation with permissive hypercapnia:a prospective study.Crit Care Med,1994,22:1568-1578.
17 The Acute Respiratory Distress Syndrome Network.Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med 2000;342:1301-1308.
18 Hirveh ER.Advance in the management of cute respiratory distress syndrome[J].Atch Surg.2000,135:126-135.
19 Halter JM,Steinberg JM,Gatto LA,et al.Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability.Crit Care.2007;11(1):R20.
20 陈惠香.机械通气对肺组织和全身炎症反应的影响[D].浙江大学,2003.
21 Amato MB,Barbas CS,Medeiros DM,et al.Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome..N Engl J Med.1998 Feb 5;338(6):347-54.
22 Lim SC,Kim YI.The role of the lactate dehydrogenase and the effect of prone position during ventilator-induced lung injury.J Korean Med Sci.2004Apr;19(2):223-8.
23 Nishimura M,Honda O,Tomiyama N,et al.Body position does not influence the location of ventilator-induced lung injury.Intensive Care Med.2000Nov;26(11):1664-9.
24 Imai Y,Kawano T,Iwamoto S,et al.Intratracheal anti-tumor necrosis factor-αantibody attenuates ventilator-induced lung injury in rabbits.J Appl Physiol,1999,87:510-515.
25 Jerng JS,Hsu YC,Wu HD.et al.Role of the renin-angiotensin system in ventilator-induced lung injury:an in vivo study in a rat model.Thorax.2007Jun;62(6):527-35.Epub 2007 Jan 18.
26 詹庆元,王辰.肺复张手法1中华结核和呼吸杂志,2001,24(6):325.
27 谢利娟,朱晓东,沈艺,等.NF-κB抑制剂对机械通气肺损伤的保护作用.中华围产医学杂志,2007年,02期.
28 WolfgangM Roemer,Stephan Gentzsch,Harald Andel,et al.Pressure Increase Due to Hydrostatic Pressure of Perfluorocarbon[J].American Journal of Respiratory and Critical Care Medicine,2006,173:1046-1047.
2 Imanaka H,Shimaoka M,Matsuura N,et al.Ventilator-induced lung injury is associated with neutrophil infiltration,macrophage activation,and TGF-beta 1mRNA upregulation in rat lungs.Anesth Analg 2001;92:428-436.
3 Yamamoto H,Termoto H,Uetani K,et al.Stretch induces a growth factor in alveolar cells via protein kinase[J].Respire Physiol,2001,127(2-3):105.
4 Tremblay L N,Slutsky A S.Ventilator-induced injury:from Barotraumas to biotrauma[J].Proc Assoc Am Physcians,1998,110(6):482-488.
5 Nonas S,Birukova AA,Fu P,et al.Oxidized phospbolipids reduce ventilator-induced vascular leak and inflammation in vivo.Crit Care.2008 Jan 24;12(1):R27.
6 Ricard JD,Dreyfuss D,Sanmon G.Ventilator-induced lung injury.Curt Opin Crit Care.2002 Feb;8(1):12-20.
7 The Acute Respiratory Distress Syndrome Network.Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med 2000;342:1301-1308.
8 Melanie J.Scott,Christopher J.Godshall,and William G.Jaks,STATs,Cytokines,and Sepsis.Clinical and Diagnostic Laboratory Immunology,November 2002,p.1153-1159.
9 弓清梅,李建强,刘卓拉.大鼠急性肺损伤过程中STAT3的活化对bcl-2 bax 表达及细胞凋亡的影响.中国药物与临床,2007年1月第7卷第1期:35-37.
10 Nin N,Lorente JA,de Paula M,et al.Rats surviving injurious mechanical ventilation show reversible pulmonary,vascular and inflammatory changes.Intensive Care Med.2008 Jan 5.
11 Rodrigues SF,de Oliveira MA,Martins JO,et al.Differential effects of chloral hydrate- and ketamine/xylazine-induced anesthesia by the s.c.route.Life Sci, 2006,79:1630-7.
12 Hu GD,Cai SX,Chen B,Chen YH.Effects of serum of the rats ventilated with high tidal volume on endothelial cell permeability and therapeutic effects of ulinastatin.Chin Med J(Engl).2006 Aug 20;119(16):1374-80.
13 Kacmarek RM.Ventilator-associated lung injury.Int Anesthesiol Clin.1999,37(3):47-64.
14 Stuber F,Wrigge H,et al.Kinetic and reversibility of mechanical ventilator-associated pulmonary and systemic inflammatory response in patients with acute lung injury[J].Inten Care Med,2002,28:834-841.
15 陈惠香.机械通气对肺组织和全身炎症反应的影响[D].浙江大学,2003.
16 Kawano T,Moil S,Cybulsky M,et al.Effect of granulocyte Depletion in a ventilated surfactant-depleted lung.J Appl Physiol.1987,62:27-33.
17 唐柚青,郭振辉,邓青南,等.小潮气量通气对机械通气导致肺损伤及多器官功能衰竭中核因子-κB活性的影响.实用医学杂志,2007年第23卷第12期:1809-11.
18 冯丹,姚尚龙,尚游,等.大鼠机械通气所致肺损伤时p 38丝裂原活化蛋白激酶通路的激活.中国危重病急救医学,2007年2月第19卷第2期:77-80.
19 Kaynar AM,Houghton AM,Lum EH,et al.Neutrophil Elastase Is Needed for Neutrophil Emigration into Lungs in Ventilator-Induced Lung Injury.Am J Respir Cell Mol Biol.2008 Feb 14.
20 Sakashita A,Nishimura Y,Nishiuma T,et al.Neutrophil elastase inhibitor (sivelestat)attenuates subsequent ventilator-induced lung injury in mice.Eur J Pharmacol.2007 Sep 24;571(1):62-71.
21 Chemoff AE,Granowitz EV Shapiro L,et al.A randomized,controlled trial of IL-10 in humans.Inhibition of inflammatory cytokine production and immune responses.J Immunol.1995,154(10):5492-9.
22 Simons Rk,Junger WG Loomis WH,et al.Acute lung injury in Endotoxemic rats is associated with sustained circulating IL-6 levels and intrapulmonary CINC activity and neutrophil recruiment-role of circulating TNF-alpha and IL-beta?hock.1996,6:39-45.
23 Fujitani Y, Hibi M, Fukada T, et al. An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT. Oncogene. 1997 Feb 20;14(7):751-61.
24 Ihle JN. The STAT family in cytokine signaling. Curr Opin Cell Boil, 2001, 13(2): 211- 217.
25 Danell JE Jr. STATs and gene regulation. Science, 1997,277 (12): 1630.
26 Scott MJ, Godshall CJ, Cheadle WG. Jaks, STATs, Cytokines, and Sepsis. Clin Diagn Lab Immunol. 2002 Nov;9(6):1153-9.
27 Zhang X, Blenis J, Li HC et al. Requirement of serine phosphorylation for formation of STAT-promoter complexes. Science. 1995 Mar 31;267(5206): 1990-4.
28 Quinton LJ, Jones MR, Robson BE, et al. Alveolar Epithelial STAT3, IL-6 Family Cytokines, and Host Defense During Escherichia coli Pneumonia. Am J Respir Cell Mol Biol. 2008 Jan 10.
29 Wang G, Qian P, Jackson FR,et al.Sequential activation of JAKs, STATs and xanthine dehydrogenase/oxidase by hypoxia in lung microvascular endothelial cells. Int J Biochem Cell Biol. 2008;40(3):461-70.
30 Matsuzaki Y, Xu Y, Ikegami M,et al. Stat3 is required for cytoprotection of the respiratory epithelium during adenoviral infection. J Immunol. 2006 Jul 1;177(1):527-37.
31 Xu Y, Ikegami M, Wang Y,et al. Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells. BMC Genomics. 2007 Dec 10;8:455.
32 Vaneker M, Halbertsma FJ, van Egmond J, et al. Mechanical ventilation in healthy mice induces reversible pulmonary and systemic cytokine elevation with preserved alveolar integrity: an in vivo model using clinical relevant ventilation settings. Anesthesiology. 2007 Sep;107(3):419-26.
33 Halter JM, Steinberg JM, Gatto LA,et al. Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability. Crit Care. 2007; 11(1):R20.
34 Amato MB,Barbas CS,Medeiros DM,et al.Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome..N Engl J Med.1998 Feb 5;338(6):347-54.
35 Hierholzer C,Kalff JC,Omert L,et al.Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury.Am J Physiol.1998 Sep;275(3 Pt 1):L611-21.
36 Severgnini M,Takahashi S,Rozo LM,et al.Activation of the STAT pathway in acute lung injury.Am J Physiol Lung Cell Mol Physiol.2004 Jun;286(6):L1282-92.
1 Tremblay LN,Slutsky AS.Ventilator-induced injury:from Barotratuma to biotrauma.Proc Assoc Am Physicians,1998,110:482-488.
2 Kawano T,Mori S,Cybulsky M,et al.Effect of granulocyte Depletion in a ventilated surfactant-depleted lung.J Appl Physiol.1987,62:27-33.
3 Zhang H,Grasso S,Downey G et al.Mechanical ventilation Activates polymorphonuclear(PMN)cells.Am J Respir Crit Care Med,2 000,161:1095-1100.
4 张新日,杜永成,姜宏英,等。肺泡巨噬细胞活化在大鼠呼吸相关肺损伤中的作用。中华结核和呼吸杂志,2006年7月第29卷第7期:482-484.
5 Pugin J,Verghese G,Widmer MC,et al.The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome.Crit Care Med,1999,27:304-312.
6 Yamamoto H,Teramoto H,Uetani K,et al.Cyclic stretch up-regulates intefleukin-8 and transforming growth factor-betal production through a protein kinase C-dependent pathway in alveolar epithelial cells.Respirology.2002 Jun;7(2):103-9.
7 von Bethmann AN,Brasch F,Nusing R,et al.Hyperventilation induces release of cytokines from perfused mouse lung.Am J Respir Crit Care Med.1998 Jan;157(1):263-72.
8 Fingar VH,Buschemeyer WC,Johnston MN,et al.Constiutive and stimulated expression of ICAM-1 protein on pulmonary endothelian cells in vivo.Microvas Res,1997,54:135-146.
9 唐柚青,郭振辉,邓青南,等.小潮气量通气对机械通气导致肺损伤及多器官功能衰竭中核因子-κB活性的影响.实用医学杂志,2007年第23卷第12期:1809-11.
10 冯丹,姚尚龙,尚游,等.大鼠机械通气所致肺损伤时p 38丝裂原活化蛋白激酶通路的激活.中国危重病急救医学,2007年2月第19卷第2期:77-80.
11 Kaynar AM,Houghton AM,Lum EH,et al.Neutrophil Elastase Is Needed for Neutrophil Emigration into Lungs in Ventilator-Induced Lung Injury.Am J Respir Cell Mol Biol.2008 Feb 14.
12 Sakashita A,Nishimura Y,Nishiuma T,et al.Neutrophil elastase inhibitor (sivelestat)attenuates subsequent ventilator-induced lung injury in mice.Eur J Pharmacol.2007 Sep 24;571(1):62-71.
13 Chernoff AE,Granowitz EV Shapiro L,et al.A randomized,controlled trial of IL-10 in humans.Inhibition of inflammatory cytokine production and immune responses.J Immunol.1995,154(10):5492-9.
14 胡国栋,蔡绍曦,陈英华,等.不同潮气量机械通气对大鼠支气管和肺组织细胞凋亡的影响.第一军医大学学报.2005;25(5):508-12.
15 Syrkina O,Jafari B,Hales CA,et al.Oxidant stress mediates inflammation and apoptosis in ventilator-induced lung injury.Respirology.2008 May;13(3):333-40.
16 Hickling KG,Walsh J,Henderson S,et al.Low mortality rate in adult respiratory distress syndrome using low-volume,pressure-limited ventilation with permissive hypercapnia:a prospective study.Crit Care Med,1994,22:1568-1578.
17 The Acute Respiratory Distress Syndrome Network.Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med 2000;342:1301-1308.
18 Hirveh ER.Advance in the management of cute respiratory distress syndrome[J].Atch Surg.2000,135:126-135.
19 Halter JM,Steinberg JM,Gatto LA,et al.Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability.Crit Care.2007;11(1):R20.
20 陈惠香.机械通气对肺组织和全身炎症反应的影响[D].浙江大学,2003.
21 Amato MB,Barbas CS,Medeiros DM,et al.Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome..N Engl J Med.1998 Feb 5;338(6):347-54.
22 Lim SC,Kim YI.The role of the lactate dehydrogenase and the effect of prone position during ventilator-induced lung injury.J Korean Med Sci.2004Apr;19(2):223-8.
23 Nishimura M,Honda O,Tomiyama N,et al.Body position does not influence the location of ventilator-induced lung injury.Intensive Care Med.2000Nov;26(11):1664-9.
24 Imai Y,Kawano T,Iwamoto S,et al.Intratracheal anti-tumor necrosis factor-αantibody attenuates ventilator-induced lung injury in rabbits.J Appl Physiol,1999,87:510-515.
25 Jerng JS,Hsu YC,Wu HD.et al.Role of the renin-angiotensin system in ventilator-induced lung injury:an in vivo study in a rat model.Thorax.2007Jun;62(6):527-35.Epub 2007 Jan 18.
26 詹庆元,王辰.肺复张手法1中华结核和呼吸杂志,2001,24(6):325.
27 谢利娟,朱晓东,沈艺,等.NF-κB抑制剂对机械通气肺损伤的保护作用.中华围产医学杂志,2007年,02期.
28 WolfgangM Roemer,Stephan Gentzsch,Harald Andel,et al.Pressure Increase Due to Hydrostatic Pressure of Perfluorocarbon[J].American Journal of Respiratory and Critical Care Medicine,2006,173:1046-1047.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |