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

目的  觀察反復(fù)吸入煙曲霉(AF)孢子對慢性阻塞性肺疾?。–OPD)大鼠氣道炎癥和重構(gòu)的影響。方法  50只Wistar大鼠隨機分為A、B、C、D及E組,每組10只。A、B、C和D組用氣管內(nèi)吸入脂多糖聯(lián)合熏香煙的方法建立COPD模型,E組為正常對照組。建模后A、B和C組分別經(jīng)鼻吸入高濃度AF孢子(1×106cfu/次)、低濃度AF孢子(1×103cfu/次)和生理鹽水100 mL,每周2次,連續(xù)5周;D組無處理。測定支氣管肺泡灌洗液(BALF)中白細胞總數(shù)及分類,白細胞介素8(IL-8)和轉(zhuǎn)化生長因子b(TGF-b)的水平;肺組織病理切片HE、PAS和Masson染色,觀察氣道炎癥并行半定量評分及病理圖像的形態(tài)學(xué)測量分析。結(jié)果  與E組比較,D組大鼠出現(xiàn)典型COPD病理改變,模型建立成功。A組和B組BALF中白細胞總數(shù)、中性粒細胞及淋巴細胞百分比均高于C組和D組(P均 lt;0.01);A組和B組BALF中的IL-8和TGF-b濃度均高于C組和D組(P均 lt;0.01);A組的氣道炎癥評分高于B、C和D組(P均 lt;0.01);A組和B組的管壁總厚度(WAt/Pbm)、平滑肌層厚度(WAm/Pbm)、管壁膠原沉積厚度(WCt/Pbm)、管壁外層膠原沉積厚度(WCo/Pbm)及杯狀細胞占上皮細胞比例均高于C組和D組(P均 lt;0.01);A組和B組BALF中IL-8與中性粒細胞百分比、氣道炎癥評分及杯狀細胞占上皮細胞百分比呈正相關(guān)(r=0.856,P lt;0.01;r=0.884,P lt;0.01;r=0.702,P lt;0.05);TGF-b與WAt/Pbm、WCt/Pbm、WCo/Pbm及杯狀細胞占上皮細胞百分比呈正相關(guān)(r=0.706,P lt;0.05;r=0.802,P lt;0.01;r=0.876,P lt;0.01;r=0.713,P lt;0.05)。結(jié)論  反復(fù)吸入AF孢子可加重COPD大鼠氣道炎癥,并促進氣道重構(gòu)。

引用本文: 高福生,龍飛,祁卉卉,張軼,金先橋. 反復(fù)吸入煙曲霉孢子對慢性阻塞性肺疾病大鼠氣道炎癥和重構(gòu)的影響. 中國呼吸與危重監(jiān)護雜志, 2008, 08(3): 205-209. doi: 復(fù)制

1. Wu L,Skinner SJ,Lambie N,et al.Immunohistochemical staining for Chlamydia pneumoniae is increased in lung tissue from subjects with chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2000,162:1148-1151.
2. Retamales I,Elliott WM,Meshi B,et al.Amplification of inflammation in emphysema and its association with latent adenoviral infection.Am J Respir Crit Care Med,2001,164:469-473.
3. Wilkinson TM,Patel IS,Wilks M,et al.Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2003,167:1090-1095.
4. Kauffman HF,Tomee JF,van de Riet MA,et al.Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production.J Allergy Clin Immunol,2000,105:1185-1193.
5. 宋一平,崔德健,茅培英,等.慢性阻塞性肺疾病大鼠模型氣道重塑及生長因子的研究.中華結(jié)核和呼吸雜志,2001,24:283-287..
6. 王妍,龍飛,祁卉卉,等.煙曲霉菌孢子對哮喘大鼠氣道炎癥和氣道反應(yīng)性的影響.中國呼吸與危重監(jiān)護雜志,2007,6:185-190.
7. Tang CM,Cohen J,Krausz T,et al.The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis.Infect Immun,1993,61:1650-1656.
8. 鐘小寧,白晶,施煥中,等.慢性支氣管炎與肺氣腫大鼠氣道炎癥與重塑的實驗研究.中華結(jié)核和呼吸雜志,2003,26:750-755.
9. Palmans E,Kips JC,Pauwels RA.Prolonged allergen exposure induces structural airway changes in sensitized rats.Am J Respir Crit Care Med,2000,161:627-635.
10. Latge JP.Aspergillus fumigatus and aspergillosis.Clin Microbiol Rev,1999,12:310-350.
11. Rivera A,Hohl T,Pamer EG.Immune response to Aspergillus fumigatus infections.Biol Blood Marrow Transplant,2006,12:47-49.
12. Garnacho-Monterol J,Amaya-Villar R,Ortiz-Leyba C,et al.Isolation of Aspergillus spp.from the respiratory tract in critically ill patients:risk factors,clinical presentation and outcome.Crit Care,2005,9:R191-R199.
13. Engelhart S,Hanfland J,Glasmacher A,et al.Impact of portable air filtration units on exposure of hematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions.J Hosp Infect,2003,54:300-304.
  1. 1. Wu L,Skinner SJ,Lambie N,et al.Immunohistochemical staining for Chlamydia pneumoniae is increased in lung tissue from subjects with chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2000,162:1148-1151.
  2. 2. Retamales I,Elliott WM,Meshi B,et al.Amplification of inflammation in emphysema and its association with latent adenoviral infection.Am J Respir Crit Care Med,2001,164:469-473.
  3. 3. Wilkinson TM,Patel IS,Wilks M,et al.Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2003,167:1090-1095.
  4. 4. Kauffman HF,Tomee JF,van de Riet MA,et al.Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production.J Allergy Clin Immunol,2000,105:1185-1193.
  5. 5. 宋一平,崔德健,茅培英,等.慢性阻塞性肺疾病大鼠模型氣道重塑及生長因子的研究.中華結(jié)核和呼吸雜志,2001,24:283-287..
  6. 6. 王妍,龍飛,祁卉卉,等.煙曲霉菌孢子對哮喘大鼠氣道炎癥和氣道反應(yīng)性的影響.中國呼吸與危重監(jiān)護雜志,2007,6:185-190.
  7. 7. Tang CM,Cohen J,Krausz T,et al.The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis.Infect Immun,1993,61:1650-1656.
  8. 8. 鐘小寧,白晶,施煥中,等.慢性支氣管炎與肺氣腫大鼠氣道炎癥與重塑的實驗研究.中華結(jié)核和呼吸雜志,2003,26:750-755.
  9. 9. Palmans E,Kips JC,Pauwels RA.Prolonged allergen exposure induces structural airway changes in sensitized rats.Am J Respir Crit Care Med,2000,161:627-635.
  10. 10. Latge JP.Aspergillus fumigatus and aspergillosis.Clin Microbiol Rev,1999,12:310-350.
  11. 11. Rivera A,Hohl T,Pamer EG.Immune response to Aspergillus fumigatus infections.Biol Blood Marrow Transplant,2006,12:47-49.
  12. 12. Garnacho-Monterol J,Amaya-Villar R,Ortiz-Leyba C,et al.Isolation of Aspergillus spp.from the respiratory tract in critically ill patients:risk factors,clinical presentation and outcome.Crit Care,2005,9:R191-R199.
  13. 13. Engelhart S,Hanfland J,Glasmacher A,et al.Impact of portable air filtration units on exposure of hematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions.J Hosp Infect,2003,54:300-304.
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