目的 研究實驗性酸吸入致肺纖維化可能的作用機制。方法 健康雄性SD大鼠120只,隨機分為正常對照組、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。博來霉素組氣管內一次性注入博來霉素誘導纖維化,鹽酸組每周氣管內滴注不同濃度鹽酸1次,正常對照組每周氣管內滴注生理鹽水1次。各組分別于造模后第7、14、28及42 d隨機處死6只,取肺組織行HE、Masson染色評價肺組織病理變化,消化法測定肺組織羥脯氨酸(HYP)含量,分別采用RT-PCR和免疫組化法測定肺組織轉化生長因子β1(TGF-β1)的mRNA和蛋白表達。結果 鹽酸組肺泡炎程度始終顯著高于對照組(P lt;0.01),在開始2周內達到一個高峰,隨后仍舊維持一個相對較高狀態(tài),從28 d達到或者超過博來霉素組水平。鹽酸組纖維化程度隨時間逐漸增強,顯著高于對照組(P lt;0.01或0.05),但始終未超過博來霉素組;第42 d時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時達到博來霉素組水平,至42 d時超過博來霉素組水平。鹽酸組TGF-β1表達水平從42 d起與博來霉素組無顯著性差異。結論 實驗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. 實驗性酸吸入致大鼠肺纖維化. 中國呼吸與危重監(jiān)護雜志, 2008, 08(5): 370-375. doi: 復制
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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系探討.中國呼吸與危重監(jiān)護雜志,2007,6:177-179,193. |
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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. |
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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)學變化的實驗研究.中國實驗動物學報,2003,11,77-80. |
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- 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系探討.中國呼吸與危重監(jiān)護雜志,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干擾素對實驗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)學變化的實驗研究.中國實驗動物學報,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.