• 南京大學(xué)醫(yī)學(xué)院附屬鼓樓醫(yī)院呼吸內(nèi)科(江蘇南京 210008);

目的  研究實(shí)驗(yàn)性酸吸入致肺纖維化可能的作用機(jī)制。方法  健康雄性SD大鼠120只,隨機(jī)分為正常對(duì)照組、博來霉素組、高濃度鹽酸組、中濃度鹽酸組和低濃度鹽酸組,每組24只。博來霉素組氣管內(nèi)一次性注入博來霉素誘導(dǎo)纖維化,鹽酸組每周氣管內(nèi)滴注不同濃度鹽酸1次,正常對(duì)照組每周氣管內(nèi)滴注生理鹽水1次。各組分別于造模后第7、14、28及42 d隨機(jī)處死6只,取肺組織行HE、Masson染色評(píng)價(jià)肺組織病理變化,消化法測(cè)定肺組織羥脯氨酸(HYP)含量,分別采用RT-PCR和免疫組化法測(cè)定肺組織轉(zhuǎn)化生長因子β1(TGF-β1)的mRNA和蛋白表達(dá)。結(jié)果  鹽酸組肺泡炎程度始終顯著高于對(duì)照組(P lt;0.01),在開始2周內(nèi)達(dá)到一個(gè)高峰,隨后仍舊維持一個(gè)相對(duì)較高狀態(tài),從28 d達(dá)到或者超過博來霉素組水平。鹽酸組纖維化程度隨時(shí)間逐漸增強(qiáng),顯著高于對(duì)照組(P lt;0.01或0.05),但始終未超過博來霉素組;第42 d時(shí)高濃度和中濃度鹽酸組與博來霉素組纖維化程度無顯著差異(P gt;0.05);而低濃度鹽酸組纖維化程度與高、中濃度組相比,早期沒有顯著差異,自42 d起與高濃度鹽酸組有明顯差異(P lt;0.05)。高、中濃度鹽酸組肺組織HYP含量自14 d起始終顯著高于對(duì)照組(P均 lt;0.05),但未超過博來霉素組;高濃度鹽酸組HYP含量在第42 d與博來霉素組無明顯差異,中、低濃度鹽酸組HYP含量始終低于博來霉素組(P均 lt;0.05)。鹽酸組肺組織TGF-β1 mRNA在28 d時(shí)達(dá)到博來霉素組水平,至42 d時(shí)超過博來霉素組水平。鹽酸組TGF-β1表達(dá)水平從42 d起與博來霉素組無顯著性差異。結(jié)論  實(shí)驗(yàn)性酸吸入可引起大鼠肺纖維化,比傳統(tǒng)的博來霉素造模方法更符合肺纖維化的病理生理過程。

引用本文: 陳石,張德平. 實(shí)驗(yàn)性酸吸入致大鼠肺纖維化. 中國呼吸與危重監(jiān)護(hù)雜志, 2008, 08(5): 370-375. doi: 復(fù)制

1. Salvioli B,Belmonte G,Stanghellini V,et al.Gastro-oesophageal reflux and interstitial lung disease.Dig Liver Dis,2006,38:879-884.
2. Raghu G,F(xiàn)reudenberger TD,Yang S,et al.High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis.Eur Respir J,2006,27:136-142.
3. Szapiel SV,Elson NA,F(xiàn)ulmer JD,et a1.Bleomycin-induced interstitial pulmonary disease in the nude,athymic mouse.Am Rev Resp Dis,1979,120:893-899.
4. Hawry?kiewicz I,P?ywaczewski R,Dziedzic D,et al.Gastroesophageal reflux disease(GERD) in patients with obstructive sleep apnoea syndrome(OSAS).Pneumonol Alergol Pol,2006,74:361-364.
5. Weldon DR.Gastroesophageal reflux disease and sinusitis:their role in patients with chronic cough.Allergy Asthma Proc,2006,27:36-44.
6. Havemann BD,Henderson CA,El-Serag HB.The association between gastro-oesophageal reflux disease and asthma:a systematic review.Gut,2007,56:1654-1664.
7. Kempainen RR,Savik K,Whelan TP,et al.High prevalence of proximal and distal gastroesophageal reflux disease in advanced COPD.Chest,2007,131:1666-1671.
8. 王萍,秦雪冰,王瑞娟,等.胃食管反流與慢性阻塞性肺疾病急性加重的關(guān)系探討.中國呼吸與危重監(jiān)護(hù)雜志,2007,6:177-179,193.
9. Mays EE,Dubois JJ,Hamilton GB.Pulmonary fibrosis associated with tracheobronchial aspiration:a study of the frequency of hiatal hernia and gastroesophageal reflux in interstitial pulmonary fibrosis of obscure etiology.Chest,1976,69:512-515.
10. Selman M,Pardo A.Role of epithelial cells in idiopathic pulmonary fibrosis:from innocent targets to serial killers.Proc Am Thorac Soc,2006,3:364-372.
11. Popper H,Juettner F,Pinter J.The gastric juice aspiration syndrome(Mendelson syndrome).Aspects of pathogenesis and treatment in the pig.Virchows Arch A Pathol Anat Histopathol,1986,409:105-117.
12. 張德平,莊誼,孟凡青,等.γ干擾素對(duì)實(shí)驗(yàn)性肺纖維化大鼠肺泡炎和肺纖維化的影響.中國呼吸與危重監(jiān)護(hù)雜志,2006,5:189-192.
13. 柴文戍,李永春,劉玉玲,等.博萊霉素致肺纖維化大鼠形態(tài)學(xué)變化的實(shí)驗(yàn)研究.中國實(shí)驗(yàn)動(dòng)物學(xué)報(bào),2003,11,77-80.
14. Bartram U,Speer CP.The role of transforming growth factor beta in lung development and disease.Chest,2004,125:754-765.
15. Allen JT,Spiteri MA.Growth factors in idiopathic pulmonary fibrosis:relative roles.Respir Res,2002,3:13-16.
  1. 1. Salvioli B,Belmonte G,Stanghellini V,et al.Gastro-oesophageal reflux and interstitial lung disease.Dig Liver Dis,2006,38:879-884.
  2. 2. Raghu G,F(xiàn)reudenberger TD,Yang S,et al.High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis.Eur Respir J,2006,27:136-142.
  3. 3. Szapiel SV,Elson NA,F(xiàn)ulmer JD,et a1.Bleomycin-induced interstitial pulmonary disease in the nude,athymic mouse.Am Rev Resp Dis,1979,120:893-899.
  4. 4. Hawry?kiewicz I,P?ywaczewski R,Dziedzic D,et al.Gastroesophageal reflux disease(GERD) in patients with obstructive sleep apnoea syndrome(OSAS).Pneumonol Alergol Pol,2006,74:361-364.
  5. 5. Weldon DR.Gastroesophageal reflux disease and sinusitis:their role in patients with chronic cough.Allergy Asthma Proc,2006,27:36-44.
  6. 6. Havemann BD,Henderson CA,El-Serag HB.The association between gastro-oesophageal reflux disease and asthma:a systematic review.Gut,2007,56:1654-1664.
  7. 7. Kempainen RR,Savik K,Whelan TP,et al.High prevalence of proximal and distal gastroesophageal reflux disease in advanced COPD.Chest,2007,131:1666-1671.
  8. 8. 王萍,秦雪冰,王瑞娟,等.胃食管反流與慢性阻塞性肺疾病急性加重的關(guān)系探討.中國呼吸與危重監(jiān)護(hù)雜志,2007,6:177-179,193.
  9. 9. Mays EE,Dubois JJ,Hamilton GB.Pulmonary fibrosis associated with tracheobronchial aspiration:a study of the frequency of hiatal hernia and gastroesophageal reflux in interstitial pulmonary fibrosis of obscure etiology.Chest,1976,69:512-515.
  10. 10. Selman M,Pardo A.Role of epithelial cells in idiopathic pulmonary fibrosis:from innocent targets to serial killers.Proc Am Thorac Soc,2006,3:364-372.
  11. 11. Popper H,Juettner F,Pinter J.The gastric juice aspiration syndrome(Mendelson syndrome).Aspects of pathogenesis and treatment in the pig.Virchows Arch A Pathol Anat Histopathol,1986,409:105-117.
  12. 12. 張德平,莊誼,孟凡青,等.γ干擾素對(duì)實(shí)驗(yàn)性肺纖維化大鼠肺泡炎和肺纖維化的影響.中國呼吸與危重監(jiān)護(hù)雜志,2006,5:189-192.
  13. 13. 柴文戍,李永春,劉玉玲,等.博萊霉素致肺纖維化大鼠形態(tài)學(xué)變化的實(shí)驗(yàn)研究.中國實(shí)驗(yàn)動(dòng)物學(xué)報(bào),2003,11,77-80.
  14. 14. Bartram U,Speer CP.The role of transforming growth factor beta in lung development and disease.Chest,2004,125:754-765.
  15. 15. Allen JT,Spiteri MA.Growth factors in idiopathic pulmonary fibrosis:relative roles.Respir Res,2002,3:13-16.
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