• 四川大學(xué)華西醫(yī)院呼吸內(nèi)科(四川成都 610041);

目的 探討γ干擾素(IFN-γ)對(duì)博萊霉素誘導(dǎo)的大鼠肺纖維化的干預(yù)作用及其可能的機(jī)制。方法 75只SD雄性大鼠隨機(jī)分為健康對(duì)照組、肺纖維化模型組、地塞米松干預(yù)組、高劑量IFN-γ干預(yù)組與低劑量IFN-γ干預(yù)組,每組15只。各組隨機(jī)分別于7,14,28 d各處死5只,收集肺組織作切片行HE及Masson染色判斷肺組織肺泡炎及肺纖維化程度,行免疫組化染色測(cè)定肺組織轉(zhuǎn)化生長(zhǎng)因子-β1(TGF-β1)、結(jié)締組織生長(zhǎng)因子(CTGF)、Ⅰ型和Ⅲ型膠原的表達(dá)水平。結(jié)果 與模型組比較,3個(gè)干預(yù)組的肺泡炎及肺纖維化程度均明顯減輕(P均 lt;0.05),肺組織TGF-β1、CTGF、Ⅰ型及Ⅲ型膠原的蛋白表達(dá)水平明顯降低(P均 lt;0.05),其中高劑量IFN-γ干預(yù)組肺組織TGF-β1、Ⅰ型及Ⅲ型膠原的蛋白表達(dá)水平較低劑量干預(yù)組更為顯著(P均 lt;0.05)。結(jié)論 IFN-γ具有與地塞米松相似的較強(qiáng)的抗纖維化效應(yīng),且不良反應(yīng)更少。機(jī)制可能為通過(guò)抑制細(xì)胞因子TGF-β1、CTGF的表達(dá)而減少肺組織中Ⅰ型及Ⅲ型膠原的生成,最終抑制肺纖維化。

引用本文: 王浩凌,謝敏,劉濤. γ干擾素對(duì)博萊霉素誘導(dǎo)的大鼠肺纖維化的干預(yù)作用. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2007, 6(2): 105-109. doi: 復(fù)制

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2. Waghray M,Cui Z,Horowitz JC,et al.Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblasts.FASEB J,2005,19:854-856.
3. Geiser T.Idiopathic pulmonary fibrosis--a disorder of alveolar wound repair? Swiss Med Wkly 2003,133:405-411.
4. Tabibzadeh S.Homeostasis of extracellular matrix by TGF-beta and lefty.Front Biosci,2002,7:d1231-d1246.
5. Kothapalli D,Grotendorst GR.CTGF modulates cell cycle progression in cAMP-arrested NRK fibroblasts.J Cell Physiol,2000,182:119-126.
6. Eickelberg O,Pansky A,Koehler E,et al.Molecular mechanisms of TGF-(beta) antagonism by interferon (gamma) and cyclosporine A in lung fibroblastis.FASEB J,2001,15:797-806.
7. Lortat-Jacob H,Esterre P,Grimaud JA.Interferon-gamma,an anti-fibrogenic cytokine which binds to heparan sulfate.Pathol Res Pract,1994,190:920-922.
8. Ziesche R,Hofbauer E,Wittmann K,et al.A preliminary study of long-term treatment with interferon gamma-1b and low dose prednisolone in patients with idiopathic pulmonary fibrosis.N Engl J Med,1999,341:1264-1269.
9. Szapiel SV,Elson NA.Fulmer JD,et al.Bleomycin-induced interstitial pulmonary disease in the nude,athymic mouse.Am Rev Respir Dis,1979,120:893-899.
10. Isaacs,A.,Lindermann,J.Virus interference.I.The interferon.Proc R Soc Lond B Biol Sci,1957,147:258-267.
11. Lasky JA,Ortiz LA.Antifibrotic therapy for the treatment of pulmonary fibrosis.Am J Med Sci,2001,322:213-221.
12. Oemar BS,Luscher TF.Connective tissue growth factor.Friend or foe? Arterioscler Thromb Vasc Biol,1997,17:1483-1489.
13. Van Hoozen BE,Grimmer KL,Marelich GP,et al.Early phase collagen synthesis in lungs of rats exposed to bleomycin.Toxicology,2000,147:1-13.
14. Thannickal VJ,Toews GB,White ES,et al.Mechanisms of pulmonary fibrosis.Annu Rev Med,2004,55:395-417.
15. 高曉方,崔社懷.干擾素γ對(duì)實(shí)驗(yàn)大鼠肺纖維化的治療作用及機(jī)制的初步研究.第三軍醫(yī)大學(xué)學(xué)報(bào),2005,27:143-145.
16. 黃山英,宋良文,劉濤,等.重組中國(guó)人γ干擾素對(duì)小鼠肺損傷的防治作用.中華結(jié)核和呼吸雜志,2005,28:760-762.
17. 孫麗,宋良文,劉濤,等.中國(guó)人γ-IFN對(duì)放射性肺纖維化的防治作用.中華放射醫(yī)學(xué)與防護(hù)雜志,2006,26:144-147.
18. 徐鈺,高占成,陳彬,等.γ-干擾素轉(zhuǎn)基因表達(dá)對(duì)不同時(shí)期博萊霉素致小鼠肺間質(zhì)纖維化的作用.中國(guó)呼吸與危重監(jiān)護(hù)雜志,2005,4:130-134.
19. Strieter RM.Pathogenesis and natural history of usual interstitial pneumonia:the whole story or the last chapter of a long novel.Chest,2005,128:526S-532S.
20. Majumdar S,Li D,Ansari T,et al.Different cytokine profiles in cryptogenic fibrosing alveolitis and fibrosing alveolitis associated with systemic sclerosis:a quantitative study of open lung biopsies.Eur Respir J,1999,14:251-257.
21. 左一俊.干擾素γ聯(lián)合糖皮質(zhì)激素治療特發(fā)性肺纖維化13例的療效觀察.南京醫(yī)科大學(xué)學(xué)報(bào),2006,26:1272-1274.
22. King TE Jr.Interferon gamma-1b for the treatment of idiopathic pulmonary fibrosis.N Engl J Med,2000,342:974-975.
23. Raghu G,Brown KK,Bradford WZ,et al.A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis.N Engl J Med,2004,350:125-133.
  1. 1. Demedts M,Costabel U.ATS/ERS international multidisciplinary consensus classification of the idiopathic interstitial pneumonias.Eur Respir J,2002,19:794-796.
  2. 2. Waghray M,Cui Z,Horowitz JC,et al.Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblasts.FASEB J,2005,19:854-856.
  3. 3. Geiser T.Idiopathic pulmonary fibrosis--a disorder of alveolar wound repair? Swiss Med Wkly 2003,133:405-411.
  4. 4. Tabibzadeh S.Homeostasis of extracellular matrix by TGF-beta and lefty.Front Biosci,2002,7:d1231-d1246.
  5. 5. Kothapalli D,Grotendorst GR.CTGF modulates cell cycle progression in cAMP-arrested NRK fibroblasts.J Cell Physiol,2000,182:119-126.
  6. 6. Eickelberg O,Pansky A,Koehler E,et al.Molecular mechanisms of TGF-(beta) antagonism by interferon (gamma) and cyclosporine A in lung fibroblastis.FASEB J,2001,15:797-806.
  7. 7. Lortat-Jacob H,Esterre P,Grimaud JA.Interferon-gamma,an anti-fibrogenic cytokine which binds to heparan sulfate.Pathol Res Pract,1994,190:920-922.
  8. 8. Ziesche R,Hofbauer E,Wittmann K,et al.A preliminary study of long-term treatment with interferon gamma-1b and low dose prednisolone in patients with idiopathic pulmonary fibrosis.N Engl J Med,1999,341:1264-1269.
  9. 9. Szapiel SV,Elson NA.Fulmer JD,et al.Bleomycin-induced interstitial pulmonary disease in the nude,athymic mouse.Am Rev Respir Dis,1979,120:893-899.
  10. 10. Isaacs,A.,Lindermann,J.Virus interference.I.The interferon.Proc R Soc Lond B Biol Sci,1957,147:258-267.
  11. 11. Lasky JA,Ortiz LA.Antifibrotic therapy for the treatment of pulmonary fibrosis.Am J Med Sci,2001,322:213-221.
  12. 12. Oemar BS,Luscher TF.Connective tissue growth factor.Friend or foe? Arterioscler Thromb Vasc Biol,1997,17:1483-1489.
  13. 13. Van Hoozen BE,Grimmer KL,Marelich GP,et al.Early phase collagen synthesis in lungs of rats exposed to bleomycin.Toxicology,2000,147:1-13.
  14. 14. Thannickal VJ,Toews GB,White ES,et al.Mechanisms of pulmonary fibrosis.Annu Rev Med,2004,55:395-417.
  15. 15. 高曉方,崔社懷.干擾素γ對(duì)實(shí)驗(yàn)大鼠肺纖維化的治療作用及機(jī)制的初步研究.第三軍醫(yī)大學(xué)學(xué)報(bào),2005,27:143-145.
  16. 16. 黃山英,宋良文,劉濤,等.重組中國(guó)人γ干擾素對(duì)小鼠肺損傷的防治作用.中華結(jié)核和呼吸雜志,2005,28:760-762.
  17. 17. 孫麗,宋良文,劉濤,等.中國(guó)人γ-IFN對(duì)放射性肺纖維化的防治作用.中華放射醫(yī)學(xué)與防護(hù)雜志,2006,26:144-147.
  18. 18. 徐鈺,高占成,陳彬,等.γ-干擾素轉(zhuǎn)基因表達(dá)對(duì)不同時(shí)期博萊霉素致小鼠肺間質(zhì)纖維化的作用.中國(guó)呼吸與危重監(jiān)護(hù)雜志,2005,4:130-134.
  19. 19. Strieter RM.Pathogenesis and natural history of usual interstitial pneumonia:the whole story or the last chapter of a long novel.Chest,2005,128:526S-532S.
  20. 20. Majumdar S,Li D,Ansari T,et al.Different cytokine profiles in cryptogenic fibrosing alveolitis and fibrosing alveolitis associated with systemic sclerosis:a quantitative study of open lung biopsies.Eur Respir J,1999,14:251-257.
  21. 21. 左一俊.干擾素γ聯(lián)合糖皮質(zhì)激素治療特發(fā)性肺纖維化13例的療效觀察.南京醫(yī)科大學(xué)學(xué)報(bào),2006,26:1272-1274.
  22. 22. King TE Jr.Interferon gamma-1b for the treatment of idiopathic pulmonary fibrosis.N Engl J Med,2000,342:974-975.
  23. 23. Raghu G,Brown KK,Bradford WZ,et al.A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis.N Engl J Med,2004,350:125-133.