• 上海交通大學(xué)附屬第一人民醫(yī)院呼吸科（上海 200080）;

現(xiàn)已認(rèn)識(shí)到免疫反應(yīng)、轉(zhuǎn)錄因子核因子κB( NF-κB) 的激活、細(xì)胞因子、中性粒細(xì)胞的激活和肺泡滲入、凝血級(jí)聯(lián)反應(yīng)、腎素-血管緊張素系統(tǒng)等多種因素構(gòu)成的復(fù)雜網(wǎng)絡(luò)參與
急性肺損傷/急性呼吸窘迫綜合征( ALI/ARDS) 的發(fā)病過(guò)程[ 1-5] 。雖然膿毒癥、創(chuàng)傷、肺炎等ALI/ARDS誘發(fā)因素很常見(jiàn), 但僅有部分病人發(fā)生ALI/ARDS, 并且具有相似臨床特
征的ALI/ARDS病人可有截然不同的結(jié)果, 這種異質(zhì)性引起研究者對(duì)影響ALI/ARDS 易感性和預(yù)后的遺傳因子進(jìn)行鑒別的濃厚興趣[ 6] 。由于數(shù)量龐大的表現(xiàn)型變異, 不完全的基
因外顯率、復(fù)雜的基因-環(huán)境相互作用及高度可能的基因座不均一性而使ALI 遺傳學(xué)的研究受到挑戰(zhàn)[ 7] 。近年來(lái)基因組學(xué)技術(shù)被應(yīng)用于ALI/ARDS 發(fā)病機(jī)制的研究, 加深了人們
對(duì)ALI/ARDS的認(rèn)識(shí)并有可能發(fā)展出新的治療策略以降低其發(fā)病率和病死率。

引用本文： 榮令,周新. 基因組學(xué)及生物信息學(xué)在ALI/ARDS發(fā)病機(jī)制中的研究進(jìn)展. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2009, 09(6): 603-606. doi: 復(fù)制

版權(quán)信息： ?四川大學(xué)華西醫(yī)院華西期刊社《中國(guó)呼吸與危重監(jiān)護(hù)雜志》版權(quán)所有，未經(jīng)授權(quán)不得轉(zhuǎn)載、改編

1. horax, 2006, 61: 621-626.
2. Belperio JA, Keane MP, Lynch JP, et al. The role of cytokines during the pathogenesis of ventilator-associated and ventilator-induced lung injury. Semin Respir Crit Care Med, 2006,27: 350-364.
3. Fudala R, Krupa A, Stankowska D, et al. Anti-interleukin-8 autoantibody: interleukin-8 immune complexes in acute lung injury /acute respiratory distress syndrome. Clin Sci ( Lond) , 2008, 114:403-412.
4. Imai Y, Kuba K, Penninger JM. The discovery of angiotensinconverting enzyme 2 and its role in acute lung injury in mice. Exp Physiol, 2008, 93: 543-548.
5. Medford AR,Millar AB. Vascular endothelial growth factor ( VEGF)in acute lung injury ( ALI) and acute respiratory distress syndrome( ARDS) : paradox or paradigm? T.
6. Schultz MJ, Haitsma JJ, Zhang H, et al. Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia--a review. Crit Care Med, 2006, 34: 871-877.
7. Villar J, Flores C, Mendez-Alvarez S. Genetic susceptibility to acute lung injury. Crit Care Med, 2003, 31: S272-275.
8. Meyer NJ, Garcia JG. Wading into the genomic pool to unravel acute lung injury genetics. Proc Am Thorac Soc, 2007, 4: 69-76.
9. Lam E, dos Santos CC. Advances in molecular acute lung injury /acute respiratory distress syndrome and ventilator-induced lung injury: the role of genomics, roteomics, bioinformatics and translational biology. Curr Opin Crit Care, 2008, 14: 3-10.
10. Cho HY, Jedlicka AE, Reddy SP, et al. Linkage analysis of susceptibility to hyperoxia. Nrf2 is a candidate gene. Am J Respir Cell Mol Biol, 2002, 26: 42-51.
11. Marzec JM, Christie JD, Reddy SP, et al. Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. FASEB J, 2007, 21: 2237-2246.
12. Marshall RP, Webb S, Bellingan GJ, et al. Angiotensin converting enzyme insertion/ deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome.Am J Respir Crit Care Med, 2002, 166: 646-650.
13. Villar J, Flores C, Perez-Mendez L, et al. Angiotensin-converting enzyme insertion/deletion polymorphism is not associated with susceptibility and outcome in sepsis and acute respiratory distress syndrome. Intensive Care Med, 2008, 34: 488-495.
14. Floros J, Veletza SV, Kotikalapudi P, et al. Dinucleotide repeats in the human surfactant protein-B gene and respiratory-distress syndrome. Biochem J, 1995, 305 ( Pt 2) : 583-590.
15. Lin Z, Pearson C, Chinchilli V, et al. Polymorphisms of human SPA,SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS. Clin Genet, 2000, 58: 181-191.
16. Wang G, Christensen ND, Wigdahl B, et al. Differences in N-linked glycosylation between human surfactant protein-B variants of the C or T allele at the single-nucleotide polymorphism at position 1580 :implications for disease. Biochem J, 2003, 369: 179-184.
17. Wurfel MM, Gordon AC, Holden TD, et al. Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. Am J Respir Crit Care Med, 2008, 178: 710-720.
18. Gao L, Grant A, Halder I, et al. Novel polymorphisms in the myosin light chain kinase gene confer risk for acute lung injury. Am J Respir Cell Mol Biol, 2006, 34: 487-495.
19. Ye SQ, Simon BA, Maloney JP, et al. Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury. Am J Respir Crit Care Med, 2005, 171: 361-370.
20. Nonas SA, Moreno-Vinasco L, Ma SF, et al. Use of consomic rats for genomic insights into ventilator-associated lung injury. AmJPhysiol Lung Cell Mol Physiol, 2007, 293: L292-302.
21. dos Santos CC, Okutani D, Hu P, et al. Differential gene profiling in acute lung injury identifies injury-specific gene expression. Crit Care Med, 2008, 36: 855-865.
22. Kamp R, Sun X, Garcia JG. Making genomics functional:deciphering the genetics of acute lung injury. Proc Am Thorac Soc,2008, 5: 348-353.
23. Wang X, Dalkic E, Wu M, et al. Gene module level analysis:identification to networks and dynamics. Curr Opin Biotechnol,2008, 19: 482-491.
24. Oti M, Brunner HG. The modular nature of genetic diseases. ClinGenet, 2007 , 71 : 1 -11.
25. 高蕓. 基于基因本體論的生物信息個(gè)人數(shù)據(jù)庫(kù)平臺(tái). 生命科學(xué)研究, 2004, 8: 65-70.
26. Gharib SA, Liles WC, Matute-Bello G, et al. Computational identification of key biological modules and transcription factors in acute lung injury. Am J Respir Crit Care Med, 2006, 173: 653-658.
27. Simon BA, Easley RB, Grigoryev DN, et al. Microarray analysis of regional cellular responses to local mechanical stress in acute lung injury. AmJ Physiol Lung Cell Mol Physiol, 2006, 291: L851-861.
28. Kamp R, Sun X, Garcia JG. Making genomics functional:deciphering the genetics of acute lung injury. Proc Am Thorac Soc ,2008, 5: 348-353.
  1. 1. horax, 2006, 61: 621-626.
  2. 2. Belperio JA, Keane MP, Lynch JP, et al. The role of cytokines during the pathogenesis of ventilator-associated and ventilator-induced lung injury. Semin Respir Crit Care Med, 2006,27: 350-364.
  3. 3. Fudala R, Krupa A, Stankowska D, et al. Anti-interleukin-8 autoantibody: interleukin-8 immune complexes in acute lung injury /acute respiratory distress syndrome. Clin Sci ( Lond) , 2008, 114:403-412.
  4. 4. Imai Y, Kuba K, Penninger JM. The discovery of angiotensinconverting enzyme 2 and its role in acute lung injury in mice. Exp Physiol, 2008, 93: 543-548.
  5. 5. Medford AR,Millar AB. Vascular endothelial growth factor ( VEGF)in acute lung injury ( ALI) and acute respiratory distress syndrome( ARDS) : paradox or paradigm? T.
  6. 6. Schultz MJ, Haitsma JJ, Zhang H, et al. Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia--a review. Crit Care Med, 2006, 34: 871-877.
  7. 7. Villar J, Flores C, Mendez-Alvarez S. Genetic susceptibility to acute lung injury. Crit Care Med, 2003, 31: S272-275.
  8. 8. Meyer NJ, Garcia JG. Wading into the genomic pool to unravel acute lung injury genetics. Proc Am Thorac Soc, 2007, 4: 69-76.
  9. 9. Lam E, dos Santos CC. Advances in molecular acute lung injury /acute respiratory distress syndrome and ventilator-induced lung injury: the role of genomics, roteomics, bioinformatics and translational biology. Curr Opin Crit Care, 2008, 14: 3-10.
  10. 10. Cho HY, Jedlicka AE, Reddy SP, et al. Linkage analysis of susceptibility to hyperoxia. Nrf2 is a candidate gene. Am J Respir Cell Mol Biol, 2002, 26: 42-51.
  11. 11. Marzec JM, Christie JD, Reddy SP, et al. Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. FASEB J, 2007, 21: 2237-2246.
  12. 12. Marshall RP, Webb S, Bellingan GJ, et al. Angiotensin converting enzyme insertion/ deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome.Am J Respir Crit Care Med, 2002, 166: 646-650.
  13. 13. Villar J, Flores C, Perez-Mendez L, et al. Angiotensin-converting enzyme insertion/deletion polymorphism is not associated with susceptibility and outcome in sepsis and acute respiratory distress syndrome. Intensive Care Med, 2008, 34: 488-495.
  14. 14. Floros J, Veletza SV, Kotikalapudi P, et al. Dinucleotide repeats in the human surfactant protein-B gene and respiratory-distress syndrome. Biochem J, 1995, 305 ( Pt 2) : 583-590.
  15. 15. Lin Z, Pearson C, Chinchilli V, et al. Polymorphisms of human SPA,SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS. Clin Genet, 2000, 58: 181-191.
  16. 16. Wang G, Christensen ND, Wigdahl B, et al. Differences in N-linked glycosylation between human surfactant protein-B variants of the C or T allele at the single-nucleotide polymorphism at position 1580 :implications for disease. Biochem J, 2003, 369: 179-184.
  17. 17. Wurfel MM, Gordon AC, Holden TD, et al. Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. Am J Respir Crit Care Med, 2008, 178: 710-720.
  18. 18. Gao L, Grant A, Halder I, et al. Novel polymorphisms in the myosin light chain kinase gene confer risk for acute lung injury. Am J Respir Cell Mol Biol, 2006, 34: 487-495.
  19. 19. Ye SQ, Simon BA, Maloney JP, et al. Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury. Am J Respir Crit Care Med, 2005, 171: 361-370.
  20. 20. Nonas SA, Moreno-Vinasco L, Ma SF, et al. Use of consomic rats for genomic insights into ventilator-associated lung injury. AmJPhysiol Lung Cell Mol Physiol, 2007, 293: L292-302.
  21. 21. dos Santos CC, Okutani D, Hu P, et al. Differential gene profiling in acute lung injury identifies injury-specific gene expression. Crit Care Med, 2008, 36: 855-865.
  22. 22. Kamp R, Sun X, Garcia JG. Making genomics functional:deciphering the genetics of acute lung injury. Proc Am Thorac Soc,2008, 5: 348-353.
  23. 23. Wang X, Dalkic E, Wu M, et al. Gene module level analysis:identification to networks and dynamics. Curr Opin Biotechnol,2008, 19: 482-491.
  24. 24. Oti M, Brunner HG. The modular nature of genetic diseases. ClinGenet, 2007 , 71 : 1 -11.
  25. 25. 高蕓. 基于基因本體論的生物信息個(gè)人數(shù)據(jù)庫(kù)平臺(tái). 生命科學(xué)研究, 2004, 8: 65-70.
  26. 26. Gharib SA, Liles WC, Matute-Bello G, et al. Computational identification of key biological modules and transcription factors in acute lung injury. Am J Respir Crit Care Med, 2006, 173: 653-658.
  27. 27. Simon BA, Easley RB, Grigoryev DN, et al. Microarray analysis of regional cellular responses to local mechanical stress in acute lung injury. AmJ Physiol Lung Cell Mol Physiol, 2006, 291: L851-861.
  28. 28. Kamp R, Sun X, Garcia JG. Making genomics functional:deciphering the genetics of acute lung injury. Proc Am Thorac Soc ,2008, 5: 348-353.

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