慢性支气管炎发病机制研究进展_West China Medical Journal

Authors：

程越 , 邱志新 ,  李为民

四川大学华西医院呼吸内科（成都 610041）;

Corresponding author：

李为民, Email: weimi003@yahoo.com

Keywords：

慢性支气管炎; 炎症机制; 氧化应激; 黏液高分泌; 气道表面脱水; 气道重塑

DOI：

10.7507/1002-0179.201510180

Video：

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Abstract Full text Figures/Tables Video References Cited by

慢性支气管炎（chronic bronchitis，CB）作为常见的气道炎症，其发病机制涉及炎症反应及相关通路、氧化应激、黏液高分泌、气道表面脱水及气道重塑等多种方式，这些机制都与慢性支气管炎的发生发展、慢性迁延等密切相关。其中炎症反应是 CB 发生发展的核心机制，除其他炎症相关因子包括肺泡表面活性蛋白、瘦素等参与外，炎症介质包括前列腺素类、激肽系统、晚期糖基化终末产物受体、活化细胞内丝裂原蛋白激酶、蛋白酶激活受体等均在炎症发生发展中起重要作用。氧化应激为炎症反应的中心环节，黏液高分泌、气道表面脱水、气道重塑等则为炎症的继发表现，其机制的阐明均对 CB 管理及转归具有重要指导意义。如何阐明各参与因素之间的关系，实现从基础研究向临床实践的转化，将成为现今一大课题。该文就慢性支气管炎相关发病机制研究进展进行了综述。

Citation： 程越, 邱志新, 李为民. 慢性支气管炎发病机制研究进展. West China Medical Journal, 2017, 32(4): 606-611. doi: 10.7507/1002-0179.201510180 Copy

1.	Barczyk A, Pierzchala W, Sozañska E. Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respir Med, 2003, 97(6): 726-733.
2.	Guddo F, Vignola AM, Saetta M, et al. Upregulation of basic fibroblast growth factor in smokers with chronic bronchitis. Eur Respir J, 2006, 27(5): 957-963.
3.	Kranenburg AR, Willems-Widyastuti A, Mooi WJ, et al. Chronic obstructive pulmonary disease is associated with enhanced bronchial expression of FGF-1, FGF-2, and FGFR-1. J Pathol, 2005, 206(1): 28-38.
4.	Oertel M, Graness A, Thim L, et al. Trefoil factor family-peptides promote migration of human bronchial epithelial cells: synergistic effect with epidermal growth factor. Am J Respir Cell Mol Biol, 2001, 25(4): 418-424.
5.	White SR. Trefoil peptides in airway epithelium: an important addition to the plethora of peptides. Am J Respir Cell Mol Biol, 2001, 25(4): 401-404.
6.	Becker S, Quay J, Koren HS, et al. Constitutive and stimulated MCP-1, GRO alpha, beta, and gamma expression in human airway epithelium and bronchoalveolar macrophages. Am J Physiol, 1994, 266(3 Pt 1): L278-L286.
7.	王慧, 程德云, 关键, 等. 单核细胞趋化蛋白-1 与 COPD 大鼠气道炎症的研究. 四川大学学报: 医学版, 2004, 35(5): 634-637.
8.	Bocchino V, Bertorelli G, Bertrand CP, et al. Eotaxin and CCR3 are up-regulated in exacerbations of chronic bronchitis. Allergy, 2002, 57(1): 17-22.
9.	蔡珊, 陈平, 朱应群, 等. 慢性阻塞性肺疾病气道炎症与肺泡巨噬细胞炎症蛋白 1α、明胶酶 B 活性的研究. 中华结核和呼吸杂志, 2001, 24(7): 429-432.
10.	Heinrich SM, Griese M. Assessment of surfactant protein A (SP-A) dependent agglutination. BMC Pulm Med, 2010, 10: 59.
11.	Starosta V, Starosta V, Griese M. Oxidative damage to surfactant protein D in pulmonary diseases. Free Radic Res, 2006, 40(4): 419-425.
12.	Tafel O, Latzin P, Paul K, et al. Surfactant proteins SP-B and SP-C and their precursors in bronchoalveolar lavages from children with acute and chronic inflammatory airway disease. BMC Pulm Med, 2008, 8: 6.
13.	Procaccini C, Jirillo E, Matarese G. Leptin as an immunomodulator. Mol Aspects Med, 2012, 33(1): 35-45.
14.	Wang B, Fu E, Cao Y, et al. Effect of leptin receptor mutation on the development of chronic bronchitis. Asia Pac J Public Health, 2013, 25(4 Suppl): 80S-87S.
15.	Stepovaia EA, Novitskiĭ VV, Riazantseva NV, et al. Chronic bronchitis: participation of red cells in the pathologic process. Klin Med (Mosk), 2004, 82(1): 53-56.
16.	Zilberman L, Rogowski O, Rozenblat M, et al. Inflammation-related erythrocyte aggregation in patients with inflammatory bowel disease. Dig Dis Sci, 2005, 50(4): 677-683.
17.	Novgorodtseva TP, Denisenko YK, Zhukova NV, et al. Modification of the fatty acid composition of the erythrocyte membrane in patients with chronic respiratory diseases. Lipids Health Dis, 2013, 12: 117.
18.	Petrache I, Petrusca DN. The involvement of sphingolipids in chronic obstructive pulmonary diseases. Handb Exp Pharmacol, 2013(216): 247-264.
19.	Gomez I, Foudi N, Longrois D, et al. The role of prostaglandin E₂ in human vascular inflammation. Prostaglandins Leukot Essent Fatty Acids, 2013, 89(2/3): 55-63.
20.	Komatsu H, Enjouji S, Ito A, et al. Prostaglandin E₂ inhibits proteinase-activated receptor 2-signal transduction through regulation of receptor internalization. J Vet Med Sci, 2013, 75(3): 255-261.
21.	Kayashima Y, Smithies O, Kakoki M. The kallikrein-kinin system and oxidative stress. Curr Opin Nephrol Hypertens, 2012, 21(1): 92-96.
22.	Zhang Y, Cardell LO, Edvinsson L, et al. MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity: a new perspective for the treatment. Pharmacol Res, 2013, 71: 9-18.
23.	Sukkar MB, Ullah MA, Gan WJ, et al. RAGE: a new frontier in chronic airways disease. Br J Pharmacol, 2012, 167(6): 1161-1176.
24.	Huang Y, Gao J, Meng XM, et al. Involvement of mitogen-activated protein kinase activation in cyclooxygenase-2 and transforming growth factor-β production in alveolar macrophage from chronic bronchitis rats. Immunopharmacol Immunotoxicol, 2011, 33(4): 645-651.
25.	Rothmeier AS, Ruf W. Protease-activated receptor 2 signaling in inflammation. Semin Immunopathol, 2012, 34(1): 133-149.
26.	Rokadia HK, Agarwal S. Serum cystatin C and emphysema: results from the National Health and Nutrition Examination Survey (NHANES) Lung, 2012, 190(3): 283-290.
27.	Piotrowski WJ, Kurmanowska Z, Antczak A, et al. Superoxide anion production by bronchoalveolar lavage cells in relation to cellular composition and lung function in sarcoidosis and chronic bronchitis. Pol Arch Med Wewn, 2009, 119(12): 777-784.
28.	Lilja-Maula LI, Palviainen MJ, Heikkilä HP, et al. Proteomic analysis of bronchoalveolar lavage fluid samples obtained from West Highland White Terriers with idiopathic pulmonary fibrosis, dogs with chronic bronchitis, and healthy dogs. Am J Vet Res, 2013, 74(1): 148-154.
29.	Nicholas BL, Skipp P, Barton S, et al. Identification of lipocalin and apolipoprotein A1 as biomarkers of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2010, 181(10): 1049-1060.
30.	Louhelainen N, Rytilä P, Haahtela T, et al. Persistence of oxidant and protease burden in the airways after smoking cessation. BMC Pulm Med, 2009, 9: 25.
31.	Macnee W. Pathogenesis of chronic obstructive pulmonary disease. Clin Chest Med, 2007, 28 (3): 479-513.
32.	Kim V, Criner GJ. Chronic bronchitis and chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2013, 187(3): 228-237.
33.	Voynow JA, Rubin BK. Mucus, and sputum. Chest, 2009, 135(2): 505-512.
34.	Morelle W, Sutton-Smith M, Morris HR, et al. FAB-MS characterization of sialyl Lewisx determinants on polylactosamine chains of human airway mucins secreted by patients suffering from cystic fibrosis or chronic bronchitis. Glycoconj J, 2001, 18(9): 699-708.
35.	Silva MA, Bercik P. Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells. Lab Invest, 2012, 92(6): 937-948.
36.	Kirkham S, Kolsum U, Rousseau K, et al. MUC5B is the major mucin in the gel phase of sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2008, 178(10): 1033-1039.
37.	Hawkins EC, Birkenheuer AJ, Marr HS, et al. Quantification of mucin gene expression in tracheobronchial epithelium of healthy dogs and dogs with chronic bronchitis. Am J Vet Res, 2007, 68(4): 435-440.
38.	Lucchini RE, Facchini F, Turato G, et al. Increased VIP-positive nerve fibers in the mucous glands of subjects with chronic bronchitis. Am J Respir Crit Care Med, 1997, 156(6): 1963-1968.
39.	Miotto D, Boschetto P, Bononi I, et al. Vasoactive intestinal peptide receptors in the airways of smokers with chronic bronchitis. Eur Respir J, 2004, 24(6): 958-963.
40.	Springer J, Groneberg DA, Pregla R, et al. Inflammatory cells as source of tachykinin-induced mucus secretion in chronic bronchitis. Regul Pept, 2005, 124(1/3): 195-201.
41.	Zhu J, Kilty I, Granger H, et al. Gene expression and immunolocalization of 15-lipoxygenase isozymes in the airway mucosa of smokers with chronic bronchitis. Am J Respir Cell Mol Biol, 2002, 27(6): 666-677.
42.	Zhu J, Majumdar S, Qiu Y, et al. Interleukin-4 and interleukin-5 gene expression and inflammation in the mucus-secreting glands and subepithelial tissue of smokers with chronic bronchitis. Lack of relationship with CD8⁺ cells. Am J Respir Crit Care Med, 2001, 164(12): 2220-2228.
43.	Anderson MP, Gregory RJ, Thompson S, et al. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science, 1991, 253(516): 202-205.
44.	Stutts MJ, Canessa CM, Olsen JC, et al. CFTR as a cAMP-dependent regulator of sodium channels. Science, 1995, 269(5225): 847-850.
45.	Mall M, Grubb BR, Harkema JR, et al. Increased airway epithelial Na⁺ absorption produces cystic fibrosis-like lung disease in mice. Nat Med, 2004, 10(5): 487-493.
46.	Mall MA, Harkema JR, Trojanek JB, et al. Development of chronic bronchitis and emphysema in beta-epithelial Na⁺ channel-overexpressing mice. Am J Respir Crit Care Med, 2008, 177(7): 730-742.
47.	Cantin AM, Hanrahan JW, Bilodeau G, et al. Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers. Am J Respir Crit Care Med, 2006, 173(10): 1139-1144.
48.	Clunes LA, Davies CM, Coakley RD, et al. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration. FASEB J, 2012, 26(2): 533-545.
49.	Marinaş AE, Ciurea P, Pirici D, et al. Chronic bronchitis: a retrospective clinicopathologic study of 25 cases. Rom J Morphol Embryol, 2012, 53(3): 503-513.
50.	Saetta M, Turato G, Facchini FM, et al. Inflammatory cells in the bronchial glands of smokers with chronic bronchitis. Am J Respir Crit Care Med, 1997, 156(5): 1633-1639.
51.	O’shaughnessy TC, Ansari TW, Barnes NC, et al. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8⁺ T lymphocytes with FEV1. Am J Respir Crit Care Med, 1997, 155(3): 852-857.
52.	Amici MD, Moratti R, Quaglini S, et al. Increased serum inflammatory markers as predictors of airway obstruction. J Asthma, 2006, 43(8): 593-596.
53.	Panzner P, Lafitte JJ, Tsicopoulos A, et al. Marked up-regulation of T lymphocytes and expression of interleukin-9 in bronchial biopsies from patients with chronic bronchitis with obstruction. Chest, 2003, 124(5): 1909-1915.
54.	Traves SL, Culpitt SV, Russell RE, et al. Increased levels of the chemokines GROalpha and MCP-1 in sputum samples from patients with COPD. Thorax, 2002, 57(7): 590-595.
55.	Bartoli ML, Di Franco A, Vagaggini BA, et al. Biological markers in induced sputum of patients with different phenotypes of chronic airway obstruction. Respiration, 2009, 77(3): 265-272.
56.	Zanini A, Chetta A, Imperatori AS, et al. The role of the bronchial microvasculature in the airway remodelling in asthma and COPD. Respir Res, 2010, 11: 132.
57.	Orihara K, Matsuda A. Pathophysiological roles of microvascular alterations in pulmonary inflammatory diseases: possible implications of tumor necrosis factor-alpha and CXC chemokines. Int J Chron Obstruct Pulmon Dis, 2008, 3(4): 619-627.
58.	李莉, 阮英茆, 陈颖, 等. 转化生长因子 β1 在吸烟诱发的地鼠慢性支气管炎与肺气肿肺组织中的表达. 中华结核和呼吸杂志, 2002, 25(5): 284-286.
59.	Duffy SM, Cruse G, Cockerill SL, et al. Engagement of the EP2 prostanoid receptor closes the K⁺ Channel KCa3.1 in human lung mast cells and attenuates their migration. Eur J Immunol, 2008, 38(9): 2548-2556.
60.	Sastre B, Fernández-Nieto M, López E, et al. PGE₂) decreases muscle cell proliferation in patients with non-asthmatic eosinophilic bronchitis. Prostaglandins Other Lipid Mediat, 2011, 95(1/4): 11-18.
61.	Polikepahad S, Moore RM, Venugopal CS. Endothelins and airways: a short review. Res Commun Mol Pathol Pharmacol, 2006, 119(1/6): 3-51.
62.	彭红, 陈平, 蔡珊. 慢性支气管炎患者肺泡巨噬细胞及诱导痰中内皮素的研究. 中华结核和呼吸杂志, 2001, 24(6): 351-354.

1. Barczyk A, Pierzchala W, Sozañska E. Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respir Med, 2003, 97(6): 726-733.
2. Guddo F, Vignola AM, Saetta M, et al. Upregulation of basic fibroblast growth factor in smokers with chronic bronchitis. Eur Respir J, 2006, 27(5): 957-963.
3. Kranenburg AR, Willems-Widyastuti A, Mooi WJ, et al. Chronic obstructive pulmonary disease is associated with enhanced bronchial expression of FGF-1, FGF-2, and FGFR-1. J Pathol, 2005, 206(1): 28-38.
4. Oertel M, Graness A, Thim L, et al. Trefoil factor family-peptides promote migration of human bronchial epithelial cells: synergistic effect with epidermal growth factor. Am J Respir Cell Mol Biol, 2001, 25(4): 418-424.
5. White SR. Trefoil peptides in airway epithelium: an important addition to the plethora of peptides. Am J Respir Cell Mol Biol, 2001, 25(4): 401-404.
6. Becker S, Quay J, Koren HS, et al. Constitutive and stimulated MCP-1, GRO alpha, beta, and gamma expression in human airway epithelium and bronchoalveolar macrophages. Am J Physiol, 1994, 266(3 Pt 1): L278-L286.
7. 王慧, 程德云, 关键, 等. 单核细胞趋化蛋白-1 与 COPD 大鼠气道炎症的研究. 四川大学学报: 医学版, 2004, 35(5): 634-637.
8. Bocchino V, Bertorelli G, Bertrand CP, et al. Eotaxin and CCR3 are up-regulated in exacerbations of chronic bronchitis. Allergy, 2002, 57(1): 17-22.
9. 蔡珊, 陈平, 朱应群, 等. 慢性阻塞性肺疾病气道炎症与肺泡巨噬细胞炎症蛋白 1α、明胶酶 B 活性的研究. 中华结核和呼吸杂志, 2001, 24(7): 429-432.
10. Heinrich SM, Griese M. Assessment of surfactant protein A (SP-A) dependent agglutination. BMC Pulm Med, 2010, 10: 59.
11. Starosta V, Starosta V, Griese M. Oxidative damage to surfactant protein D in pulmonary diseases. Free Radic Res, 2006, 40(4): 419-425.
12. Tafel O, Latzin P, Paul K, et al. Surfactant proteins SP-B and SP-C and their precursors in bronchoalveolar lavages from children with acute and chronic inflammatory airway disease. BMC Pulm Med, 2008, 8: 6.
13. Procaccini C, Jirillo E, Matarese G. Leptin as an immunomodulator. Mol Aspects Med, 2012, 33(1): 35-45.
14. Wang B, Fu E, Cao Y, et al. Effect of leptin receptor mutation on the development of chronic bronchitis. Asia Pac J Public Health, 2013, 25(4 Suppl): 80S-87S.
15. Stepovaia EA, Novitskiĭ VV, Riazantseva NV, et al. Chronic bronchitis: participation of red cells in the pathologic process. Klin Med (Mosk), 2004, 82(1): 53-56.
16. Zilberman L, Rogowski O, Rozenblat M, et al. Inflammation-related erythrocyte aggregation in patients with inflammatory bowel disease. Dig Dis Sci, 2005, 50(4): 677-683.
17. Novgorodtseva TP, Denisenko YK, Zhukova NV, et al. Modification of the fatty acid composition of the erythrocyte membrane in patients with chronic respiratory diseases. Lipids Health Dis, 2013, 12: 117.
18. Petrache I, Petrusca DN. The involvement of sphingolipids in chronic obstructive pulmonary diseases. Handb Exp Pharmacol, 2013(216): 247-264.
19. Gomez I, Foudi N, Longrois D, et al. The role of prostaglandin E₂ in human vascular inflammation. Prostaglandins Leukot Essent Fatty Acids, 2013, 89(2/3): 55-63.
20. Komatsu H, Enjouji S, Ito A, et al. Prostaglandin E₂ inhibits proteinase-activated receptor 2-signal transduction through regulation of receptor internalization. J Vet Med Sci, 2013, 75(3): 255-261.
21. Kayashima Y, Smithies O, Kakoki M. The kallikrein-kinin system and oxidative stress. Curr Opin Nephrol Hypertens, 2012, 21(1): 92-96.
22. Zhang Y, Cardell LO, Edvinsson L, et al. MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity: a new perspective for the treatment. Pharmacol Res, 2013, 71: 9-18.
23. Sukkar MB, Ullah MA, Gan WJ, et al. RAGE: a new frontier in chronic airways disease. Br J Pharmacol, 2012, 167(6): 1161-1176.
24. Huang Y, Gao J, Meng XM, et al. Involvement of mitogen-activated protein kinase activation in cyclooxygenase-2 and transforming growth factor-β production in alveolar macrophage from chronic bronchitis rats. Immunopharmacol Immunotoxicol, 2011, 33(4): 645-651.
25. Rothmeier AS, Ruf W. Protease-activated receptor 2 signaling in inflammation. Semin Immunopathol, 2012, 34(1): 133-149.
26. Rokadia HK, Agarwal S. Serum cystatin C and emphysema: results from the National Health and Nutrition Examination Survey (NHANES) Lung, 2012, 190(3): 283-290.
27. Piotrowski WJ, Kurmanowska Z, Antczak A, et al. Superoxide anion production by bronchoalveolar lavage cells in relation to cellular composition and lung function in sarcoidosis and chronic bronchitis. Pol Arch Med Wewn, 2009, 119(12): 777-784.
28. Lilja-Maula LI, Palviainen MJ, Heikkilä HP, et al. Proteomic analysis of bronchoalveolar lavage fluid samples obtained from West Highland White Terriers with idiopathic pulmonary fibrosis, dogs with chronic bronchitis, and healthy dogs. Am J Vet Res, 2013, 74(1): 148-154.
29. Nicholas BL, Skipp P, Barton S, et al. Identification of lipocalin and apolipoprotein A1 as biomarkers of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2010, 181(10): 1049-1060.
30. Louhelainen N, Rytilä P, Haahtela T, et al. Persistence of oxidant and protease burden in the airways after smoking cessation. BMC Pulm Med, 2009, 9: 25.
31. Macnee W. Pathogenesis of chronic obstructive pulmonary disease. Clin Chest Med, 2007, 28 (3): 479-513.
32. Kim V, Criner GJ. Chronic bronchitis and chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2013, 187(3): 228-237.
33. Voynow JA, Rubin BK. Mucus, and sputum. Chest, 2009, 135(2): 505-512.
34. Morelle W, Sutton-Smith M, Morris HR, et al. FAB-MS characterization of sialyl Lewisx determinants on polylactosamine chains of human airway mucins secreted by patients suffering from cystic fibrosis or chronic bronchitis. Glycoconj J, 2001, 18(9): 699-708.
35. Silva MA, Bercik P. Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells. Lab Invest, 2012, 92(6): 937-948.
36. Kirkham S, Kolsum U, Rousseau K, et al. MUC5B is the major mucin in the gel phase of sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2008, 178(10): 1033-1039.
37. Hawkins EC, Birkenheuer AJ, Marr HS, et al. Quantification of mucin gene expression in tracheobronchial epithelium of healthy dogs and dogs with chronic bronchitis. Am J Vet Res, 2007, 68(4): 435-440.
38. Lucchini RE, Facchini F, Turato G, et al. Increased VIP-positive nerve fibers in the mucous glands of subjects with chronic bronchitis. Am J Respir Crit Care Med, 1997, 156(6): 1963-1968.
39. Miotto D, Boschetto P, Bononi I, et al. Vasoactive intestinal peptide receptors in the airways of smokers with chronic bronchitis. Eur Respir J, 2004, 24(6): 958-963.
40. Springer J, Groneberg DA, Pregla R, et al. Inflammatory cells as source of tachykinin-induced mucus secretion in chronic bronchitis. Regul Pept, 2005, 124(1/3): 195-201.
41. Zhu J, Kilty I, Granger H, et al. Gene expression and immunolocalization of 15-lipoxygenase isozymes in the airway mucosa of smokers with chronic bronchitis. Am J Respir Cell Mol Biol, 2002, 27(6): 666-677.
42. Zhu J, Majumdar S, Qiu Y, et al. Interleukin-4 and interleukin-5 gene expression and inflammation in the mucus-secreting glands and subepithelial tissue of smokers with chronic bronchitis. Lack of relationship with CD8⁺ cells. Am J Respir Crit Care Med, 2001, 164(12): 2220-2228.
43. Anderson MP, Gregory RJ, Thompson S, et al. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science, 1991, 253(516): 202-205.
44. Stutts MJ, Canessa CM, Olsen JC, et al. CFTR as a cAMP-dependent regulator of sodium channels. Science, 1995, 269(5225): 847-850.
45. Mall M, Grubb BR, Harkema JR, et al. Increased airway epithelial Na⁺ absorption produces cystic fibrosis-like lung disease in mice. Nat Med, 2004, 10(5): 487-493.
46. Mall MA, Harkema JR, Trojanek JB, et al. Development of chronic bronchitis and emphysema in beta-epithelial Na⁺ channel-overexpressing mice. Am J Respir Crit Care Med, 2008, 177(7): 730-742.
47. Cantin AM, Hanrahan JW, Bilodeau G, et al. Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers. Am J Respir Crit Care Med, 2006, 173(10): 1139-1144.
48. Clunes LA, Davies CM, Coakley RD, et al. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration. FASEB J, 2012, 26(2): 533-545.
49. Marinaş AE, Ciurea P, Pirici D, et al. Chronic bronchitis: a retrospective clinicopathologic study of 25 cases. Rom J Morphol Embryol, 2012, 53(3): 503-513.
50. Saetta M, Turato G, Facchini FM, et al. Inflammatory cells in the bronchial glands of smokers with chronic bronchitis. Am J Respir Crit Care Med, 1997, 156(5): 1633-1639.
51. O’shaughnessy TC, Ansari TW, Barnes NC, et al. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8⁺ T lymphocytes with FEV1. Am J Respir Crit Care Med, 1997, 155(3): 852-857.
52. Amici MD, Moratti R, Quaglini S, et al. Increased serum inflammatory markers as predictors of airway obstruction. J Asthma, 2006, 43(8): 593-596.
53. Panzner P, Lafitte JJ, Tsicopoulos A, et al. Marked up-regulation of T lymphocytes and expression of interleukin-9 in bronchial biopsies from patients with chronic bronchitis with obstruction. Chest, 2003, 124(5): 1909-1915.
54. Traves SL, Culpitt SV, Russell RE, et al. Increased levels of the chemokines GROalpha and MCP-1 in sputum samples from patients with COPD. Thorax, 2002, 57(7): 590-595.
55. Bartoli ML, Di Franco A, Vagaggini BA, et al. Biological markers in induced sputum of patients with different phenotypes of chronic airway obstruction. Respiration, 2009, 77(3): 265-272.
56. Zanini A, Chetta A, Imperatori AS, et al. The role of the bronchial microvasculature in the airway remodelling in asthma and COPD. Respir Res, 2010, 11: 132.
57. Orihara K, Matsuda A. Pathophysiological roles of microvascular alterations in pulmonary inflammatory diseases: possible implications of tumor necrosis factor-alpha and CXC chemokines. Int J Chron Obstruct Pulmon Dis, 2008, 3(4): 619-627.
58. 李莉, 阮英茆, 陈颖, 等. 转化生长因子 β1 在吸烟诱发的地鼠慢性支气管炎与肺气肿肺组织中的表达. 中华结核和呼吸杂志, 2002, 25(5): 284-286.
59. Duffy SM, Cruse G, Cockerill SL, et al. Engagement of the EP2 prostanoid receptor closes the K⁺ Channel KCa3.1 in human lung mast cells and attenuates their migration. Eur J Immunol, 2008, 38(9): 2548-2556.
60. Sastre B, Fernández-Nieto M, López E, et al. PGE₂) decreases muscle cell proliferation in patients with non-asthmatic eosinophilic bronchitis. Prostaglandins Other Lipid Mediat, 2011, 95(1/4): 11-18.
61. Polikepahad S, Moore RM, Venugopal CS. Endothelins and airways: a short review. Res Commun Mol Pathol Pharmacol, 2006, 119(1/6): 3-51.
62. 彭红, 陈平, 蔡珊. 慢性支气管炎患者肺泡巨噬细胞及诱导痰中内皮素的研究. 中华结核和呼吸杂志, 2001, 24(6): 351-354.

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West China Medical Journal

慢性支气管炎发病机制研究进展

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