• 川北醫(yī)學院附屬醫(yī)院急診科,四川南充 637000;

急性肺損傷(acute lung injury,ALI)是臨床常見的呼吸系統(tǒng)急危重癥,其發(fā)病機制復雜,病死率高。腫瘤壞死因子α(tumor necrosis factor-α,TNF-α)是ALI發(fā)生、發(fā)展過程中非常重要的細胞因子。本文就TNF-α在ALI中的作用和以抗TNF-α為靶點治療ALI的相關研究進行綜述。

引用本文： 李孟秦 綜述 曹小平 審校. 以TNF-α為靶點治療急性肺損傷的研究進展. 華西醫(yī)學, 2009, 24(7): 1896-1899. doi: 復制

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2.
3.
4. SEMENZATO G. Tumor necrosis factor: a cytokine with multiple biological activities[J]. Br J Cancer,1990,61:354-361..
5. 章敬波,林建銀,楊恬.醫(yī)學細胞分子生物學[M].第1版.北京:中國協(xié)和醫(yī)科大學出版社,2002:6548-5494..
6. 金惠銘,盧建,殷蓮華.細胞分子病理生理學[M].第1版.鄭州:鄭州大學出版社,2002:173-174..
7. 劉紅菊,李元桂,畢愛華.腫瘤壞死因子在急性肺損傷發(fā)病機制中的作用[J].國外醫(yī)學免疫分冊,1996,(5):229-231..
8. OKAJIMA K. Regulation of inflammatory responses by endothelial cellsunderstanding the molecular mechanism(s) and its therapeutic application to sepsis[J]. Masui,2008,57(3):311-20..
9. VELDHUIZEN E J, HAAGSMAN H P. Role of pulmonary surfactant components in surface film formation and dynamics[J]. Biochim Biophys Acta,2000,1467(2):255-270..
10. BERHANE K, MARGANA R K, BOGGARAM V. Characterization of rabbit SPB promoter region responsive to downregulation by tumor necrosis factoralpha[J]. Am J Physiol Lung Cell Mol Physiol,2000,279(5):L806-814..
11. MIAKOTINA O L, SNYDER J M. TNFalpha inhibits SPA gene expression in lung epithelial cells via p38 MAPK[J]. Am J Physiol Lung Cell Mol Physiol,2002,283(2):L418-427..
12. WILCOX P, MILLIKEN C, BRESSLER B. Highdose tumor necrosis factor alpha produces an impairment of hamster diaphragm contractility. Attenuation with a prostaglandin inhibitor[J]. Am J Respir Crit Care Med,1996,153(5):1611-1615..
13. WILCOX P, OSBORNE S, BRESSLER B. Monocyte inflammatory mediators impair in vitro hamster diaphragm contractility[J]. Am Rev Respir Dis,1992,146(2):462-466..
14. SHERIDAN B C, MCINTYRE R C, MELDRUM D R, et al. Pentoxifylline treatment attenuates pulmonary vasomotor dysfunction in acute lung injury[J]. J Surg Res,1997,71(2):150-154..
15. MEDURI G U, KOHLER G, HEADLEY S, et al. Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome[J]. Chest,1995,108(5):1303-1314..
16. PARSONS P E, MATTHAY M A, WARE L B, et al. Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury[J]. Am J Physiol Lung Cell Mol Physiol,2005,288(3):L426-431..
17. VAN RIEMSDIJKVAN OVERBEEKE I C, BAAN C C, NIESTERS H G M, et al. The TNFalpha system in heart failure and after heart transplantation: plasma protein levels, mRNA expression, soluble receptors and plasma buffer capacity[J]. Eur Heart J,1999,20(11):833-840..
18. BOYLE E M Jr, CANTY T G Jr, MORGAN E N, et al. Treating myocardial ischemiareperfsion injury by targeting endothelial cell transcription[J]. Ann Thorac Surg,1999,68(5):19491953..
19. SATO Y, HIRAMATSU Y, HOMMA S, et al. Phosphodiesterase type 4 inhibitor rolipram inhibits actibation of monocytes during extracorporeal circulation[J]. J Thorac Cardiovasc Surg,2005,130(2):346-350..
20. SOUZA D G, CASSALI G D, POOLE S, et al. Effects of inhibition of PDE4 and TNFα on local and remote injuries following ischaemia and reperfusion injury[J]. Br J Pharmacol,2001,134(5):985-994. doi: 10.1038/sj.bjp.0704336..
21. MALAZDREWICH C, THUMBIKAT P, ABRAHAMSEN M S, et al. Pharmacological inhibition of Mannheimia haemolytica lipopolysaccharide and leukotoxininduced cytokine expression in bovine alveolar macrophages[J]. Microb Pathog,2004,36(3):159-169..
22. RBE C E, WILFERT F, UTHE D, et al. Modulation of radiationinduced tumor necrosis factor α (TNF-α) expression in the lung tissue pentoxifylline[J]. Radiother Oncol,2002,64(2):177-187.
23. RUIZORTEGA M, LORENZO O, SUZUKI Y, et al. Proinflammatory actions of angiotensins[J]. Curr Opin Nephrol Hypertens,2001,10(3):321-329..
24. YAO H W, MAO L G, ZHU J P. Protective effects of pravastatin in murine lipopolysaccharideinduced acue lung injury[J]. Clin Experiment Pharmacol Physiol,2006,33(9):793-797..
25. GRIP O, JANCIAUSKIENE S, LINDGREN S. Pravastatin downregulates inflammatory mediators in human monocytes in vitro[J]. Eur J Pharmacol,2000,410(1):83-92..
26. AMATO R J. Thalidomide: an antineoplastic agent[J]. Curr Oncol Rep,2002,4(1):56-62..
27. MOREIRA A L, SAMPAIO E P, ZMUIDZINAS A, et al. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation[J]. J Exp Med,1993,177(6):1675-1680. doi: 10.1084/jem.177.6.16A75..
28. ROCHA A C, FERNANDES E S, QUINTO N L, et al. Relevance of tumour necrosis factorα for the inflammatory and nociceptive responses evoked by carrageenan in the mouse paw[J]. Br J Pharmacol,2006,148(5):688-695..
29. MUKHOPADHYAY S, HOIDAL J R, MUKHERJEE T K. Role of TNFα in pulmonary pathophysiology[J]. Respir Res,2006,7(1):125-127..
30. GEARING A J, BECKETT P, CHRISTODOULOU M, et al. Processing of tumour necrosis factoralpha precursor by metalloproteinases[J]. Nature,1994,370(6490):555-557..
31. CORBEL M, LANCHOU J, GERMAIN N, et al. Modulation of airway remodelingassociated mediators by the antifibrotic compound, pirfenidone, and the matrix metalloproteinase inhibitor, batimastat, during acute lung injury in mice[J]. Eur J Pharmacol,2001,426(1-2):113-121..
32. EBERT E C. Infliximab and the TNFα system[J]. Am J Phisiol Gastrointest Liver Physiol,2009,296(3):G612-620..
33. MUTLU G M, MUTLU E A, BELLMEYER A, et al. Pulmonary adverse events of antitumor necrosis factorα antibody therapy[J]. Am J Med,2006,119(8):639-646; Comment in: Am J Med,2007,120(12):e21; author reply e23..
  1. 1.
  2. 2.
  3. 3.
  4. 4. SEMENZATO G. Tumor necrosis factor: a cytokine with multiple biological activities[J]. Br J Cancer,1990,61:354-361..
  5. 5. 章敬波,林建銀,楊恬.醫(yī)學細胞分子生物學[M].第1版.北京:中國協(xié)和醫(yī)科大學出版社,2002:6548-5494..
  6. 6. 金惠銘,盧建,殷蓮華.細胞分子病理生理學[M].第1版.鄭州:鄭州大學出版社,2002:173-174..
  7. 7. 劉紅菊,李元桂,畢愛華.腫瘤壞死因子在急性肺損傷發(fā)病機制中的作用[J].國外醫(yī)學免疫分冊,1996,(5):229-231..
  8. 8. OKAJIMA K. Regulation of inflammatory responses by endothelial cellsunderstanding the molecular mechanism(s) and its therapeutic application to sepsis[J]. Masui,2008,57(3):311-20..
  9. 9. VELDHUIZEN E J, HAAGSMAN H P. Role of pulmonary surfactant components in surface film formation and dynamics[J]. Biochim Biophys Acta,2000,1467(2):255-270..
  10. 10. BERHANE K, MARGANA R K, BOGGARAM V. Characterization of rabbit SPB promoter region responsive to downregulation by tumor necrosis factoralpha[J]. Am J Physiol Lung Cell Mol Physiol,2000,279(5):L806-814..
  11. 11. MIAKOTINA O L, SNYDER J M. TNFalpha inhibits SPA gene expression in lung epithelial cells via p38 MAPK[J]. Am J Physiol Lung Cell Mol Physiol,2002,283(2):L418-427..
  12. 12. WILCOX P, MILLIKEN C, BRESSLER B. Highdose tumor necrosis factor alpha produces an impairment of hamster diaphragm contractility. Attenuation with a prostaglandin inhibitor[J]. Am J Respir Crit Care Med,1996,153(5):1611-1615..
  13. 13. WILCOX P, OSBORNE S, BRESSLER B. Monocyte inflammatory mediators impair in vitro hamster diaphragm contractility[J]. Am Rev Respir Dis,1992,146(2):462-466..
  14. 14. SHERIDAN B C, MCINTYRE R C, MELDRUM D R, et al. Pentoxifylline treatment attenuates pulmonary vasomotor dysfunction in acute lung injury[J]. J Surg Res,1997,71(2):150-154..
  15. 15. MEDURI G U, KOHLER G, HEADLEY S, et al. Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome[J]. Chest,1995,108(5):1303-1314..
  16. 16. PARSONS P E, MATTHAY M A, WARE L B, et al. Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury[J]. Am J Physiol Lung Cell Mol Physiol,2005,288(3):L426-431..
  17. 17. VAN RIEMSDIJKVAN OVERBEEKE I C, BAAN C C, NIESTERS H G M, et al. The TNFalpha system in heart failure and after heart transplantation: plasma protein levels, mRNA expression, soluble receptors and plasma buffer capacity[J]. Eur Heart J,1999,20(11):833-840..
  18. 18. BOYLE E M Jr, CANTY T G Jr, MORGAN E N, et al. Treating myocardial ischemiareperfsion injury by targeting endothelial cell transcription[J]. Ann Thorac Surg,1999,68(5):19491953..
  19. 19. SATO Y, HIRAMATSU Y, HOMMA S, et al. Phosphodiesterase type 4 inhibitor rolipram inhibits actibation of monocytes during extracorporeal circulation[J]. J Thorac Cardiovasc Surg,2005,130(2):346-350..
  20. 20. SOUZA D G, CASSALI G D, POOLE S, et al. Effects of inhibition of PDE4 and TNFα on local and remote injuries following ischaemia and reperfusion injury[J]. Br J Pharmacol,2001,134(5):985-994. doi: 10.1038/sj.bjp.0704336..
  21. 21. MALAZDREWICH C, THUMBIKAT P, ABRAHAMSEN M S, et al. Pharmacological inhibition of Mannheimia haemolytica lipopolysaccharide and leukotoxininduced cytokine expression in bovine alveolar macrophages[J]. Microb Pathog,2004,36(3):159-169..
  22. 22. RBE C E, WILFERT F, UTHE D, et al. Modulation of radiationinduced tumor necrosis factor α (TNF-α) expression in the lung tissue pentoxifylline[J]. Radiother Oncol,2002,64(2):177-187.
  23. 23. RUIZORTEGA M, LORENZO O, SUZUKI Y, et al. Proinflammatory actions of angiotensins[J]. Curr Opin Nephrol Hypertens,2001,10(3):321-329..
  24. 24. YAO H W, MAO L G, ZHU J P. Protective effects of pravastatin in murine lipopolysaccharideinduced acue lung injury[J]. Clin Experiment Pharmacol Physiol,2006,33(9):793-797..
  25. 25. GRIP O, JANCIAUSKIENE S, LINDGREN S. Pravastatin downregulates inflammatory mediators in human monocytes in vitro[J]. Eur J Pharmacol,2000,410(1):83-92..
  26. 26. AMATO R J. Thalidomide: an antineoplastic agent[J]. Curr Oncol Rep,2002,4(1):56-62..
  27. 27. MOREIRA A L, SAMPAIO E P, ZMUIDZINAS A, et al. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation[J]. J Exp Med,1993,177(6):1675-1680. doi: 10.1084/jem.177.6.16A75..
  28. 28. ROCHA A C, FERNANDES E S, QUINTO N L, et al. Relevance of tumour necrosis factorα for the inflammatory and nociceptive responses evoked by carrageenan in the mouse paw[J]. Br J Pharmacol,2006,148(5):688-695..
  29. 29. MUKHOPADHYAY S, HOIDAL J R, MUKHERJEE T K. Role of TNFα in pulmonary pathophysiology[J]. Respir Res,2006,7(1):125-127..
  30. 30. GEARING A J, BECKETT P, CHRISTODOULOU M, et al. Processing of tumour necrosis factoralpha precursor by metalloproteinases[J]. Nature,1994,370(6490):555-557..
  31. 31. CORBEL M, LANCHOU J, GERMAIN N, et al. Modulation of airway remodelingassociated mediators by the antifibrotic compound, pirfenidone, and the matrix metalloproteinase inhibitor, batimastat, during acute lung injury in mice[J]. Eur J Pharmacol,2001,426(1-2):113-121..
  32. 32. EBERT E C. Infliximab and the TNFα system[J]. Am J Phisiol Gastrointest Liver Physiol,2009,296(3):G612-620..
  33. 33. MUTLU G M, MUTLU E A, BELLMEYER A, et al. Pulmonary adverse events of antitumor necrosis factorα antibody therapy[J]. Am J Med,2006,119(8):639-646; Comment in: Am J Med,2007,120(12):e21; author reply e23..