李偉峰 1 , 李理 1 , 袁偉鋒 1,2 , 徐虹 1 , 黃文杰 1
  • 1 廣州軍區(qū)廣州總醫(yī)院呼吸內(nèi)科( 廣東廣州510010) ;;
  • 2 南方醫(yī)科大學(xué)研究生學(xué)院( 廣東廣州510515)通訊作者: 李理, E-mail: lili_china@ 163. com;

目的  比較兩種表皮生長因子受體酪氨酸激酶抑制劑( EGFR-TKI) 吉非替尼與厄羅替尼對博萊霉素致小鼠肺纖維化的干預(yù)作用。方法  40 只雌性BALB/ c 小鼠分為對照組( NS 組) 、博萊霉素纖維化組( BLM組) 、吉非替尼組( GE 組) 和厄羅替尼組( ER 組) 。實驗第1 d, BLM組、GE 組和ER 組小鼠經(jīng)氣管滴入博萊霉素致肺纖維化, NS 組氣管內(nèi)滴入生理鹽水; 同時, GE 組及ER 組分別口服吉非替尼( 20 mg·kg- 1·d - 1 ) 和厄羅替尼( 25 mg·kg- 1· d- 1 ) , 余兩組口服生理鹽水。持續(xù)給藥2 周后殺鼠取肺, 左肺石蠟包埋切片行HE 染色與Masson 染色, 免疫組化檢測總EGFR 及磷酸化EGFR; 右肺勻漿檢測羥脯氨酸含量。結(jié)果 吉非替尼與厄羅替尼均能明顯減輕博萊霉素引起的肺結(jié)構(gòu)破壞、膠原沉積, 降低磷酸化EGFR 表達(dá)及纖維化小鼠肺羥脯氨酸含量( P  lt;0. 05) , 兩者的上述作用無明顯差異( P  gt;0. 05) 。結(jié)論  EGFR-TKI 通過抑制EGFR 磷酸化, 有效減輕博萊霉素誘導(dǎo)的肺纖維化形成, 為肺纖維化的靶向治療提供了新思路。

引用本文： 李偉峰,李理,袁偉鋒,徐虹,黃文杰. 兩種表皮生長因子受體酪氨酸激酶抑制劑對小鼠肺纖維化的干預(yù)作用比較. 中國呼吸與危重監(jiān)護(hù)雜志, 2010, 9(4): 426-429. doi: 復(fù)制

1. Carter CA, Kelly RJ, Giaccone G. Small-molecule inhibitors of the human epidermal receptor family. Expert Opin Investig Drugs,2009, 18: 1829-1842 .
2. Erp NP, Gelderblom H, Guchelaar HJ. Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev, 2009, 35 : 692-706.
3. Ashcroft T, Simpson JM, Timbrell V. Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol,1988, 41: 467-470 .
4. 李元桂, 蔡向陽, 車東媛, 等. 肺纖維化大鼠肺內(nèi)血小板源生長因子受體的表達(dá)及黃芪對其的影響. 同濟醫(yī)科大學(xué)學(xué)報, 2000 ,29( 增刊) : 119 -121.
5. Rice AB, Moomaw CR, Morgan DL, et al. Specific inhibitors of platelet-derived growth factor or epidermal growth factor receptor tyrosine kinase reduce pulmonary fibrosis in rats. Am J Pathol,1999, 155: 213-221.
6. Hardie WD, Le Cras TD, Jiang K, et al. Conditional expression of transforming growth factor-alpha in adult mouse lung causes pulmonary fibrosis. AmJ Physiol Lung Cell Mol Physiol, 2004, 286 :L741-L749 .
7. Nethery DE, Moore BB, Minowada G, et al. Expression of mutant human epidermal receptor 3 attenuates lung fibrosis and improves survival in mice. J Appl Physiol, 2005, 99 : 298-307.
8. Kudoh S, Kato H, Nishiwaki Y, et al. Interstitial lung disease in Japanese patients with lung cancer. Am J Respir Crit Care Med,2008, 177: 1348-1357.
9. Takano T, Ohe Y, Kusumoto M, et al. Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib.Lung Cancer, 2004 , 45: 93-104 .
10. Cohen MH, Johnson JR, Chen YF, et al. FDA drug approval summary: elotinib ( Tarceva) tablets. Oncologist, 2005, 10 : 461 -466.
11. Shepherd FA, Rodrigues PJ, Cinleanu T, et al. Erlotinib in previously treaded non-small-cell lung cancer. N Engl J Med, 2005 ,353: 123-132.
12. Lee E, Yi JY, Chung E, et al. Transforming growth factor beta1 transactivates EGFR via an H2 O2 -dependent mechanism in squamous carcinoma cell line. Cancer Letters, 2010, 290: 43-48.
  1. 1. Carter CA, Kelly RJ, Giaccone G. Small-molecule inhibitors of the human epidermal receptor family. Expert Opin Investig Drugs,2009, 18: 1829-1842 .
  2. 2. Erp NP, Gelderblom H, Guchelaar HJ. Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev, 2009, 35 : 692-706.
  3. 3. Ashcroft T, Simpson JM, Timbrell V. Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol,1988, 41: 467-470 .
  4. 4. 李元桂, 蔡向陽, 車東媛, 等. 肺纖維化大鼠肺內(nèi)血小板源生長因子受體的表達(dá)及黃芪對其的影響. 同濟醫(yī)科大學(xué)學(xué)報, 2000 ,29( 增刊) : 119 -121.
  5. 5. Rice AB, Moomaw CR, Morgan DL, et al. Specific inhibitors of platelet-derived growth factor or epidermal growth factor receptor tyrosine kinase reduce pulmonary fibrosis in rats. Am J Pathol,1999, 155: 213-221.
  6. 6. Hardie WD, Le Cras TD, Jiang K, et al. Conditional expression of transforming growth factor-alpha in adult mouse lung causes pulmonary fibrosis. AmJ Physiol Lung Cell Mol Physiol, 2004, 286 :L741-L749 .
  7. 7. Nethery DE, Moore BB, Minowada G, et al. Expression of mutant human epidermal receptor 3 attenuates lung fibrosis and improves survival in mice. J Appl Physiol, 2005, 99 : 298-307.
  8. 8. Kudoh S, Kato H, Nishiwaki Y, et al. Interstitial lung disease in Japanese patients with lung cancer. Am J Respir Crit Care Med,2008, 177: 1348-1357.
  9. 9. Takano T, Ohe Y, Kusumoto M, et al. Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib.Lung Cancer, 2004 , 45: 93-104 .
  10. 10. Cohen MH, Johnson JR, Chen YF, et al. FDA drug approval summary: elotinib ( Tarceva) tablets. Oncologist, 2005, 10 : 461 -466.
  11. 11. Shepherd FA, Rodrigues PJ, Cinleanu T, et al. Erlotinib in previously treaded non-small-cell lung cancer. N Engl J Med, 2005 ,353: 123-132.
  12. 12. Lee E, Yi JY, Chung E, et al. Transforming growth factor beta1 transactivates EGFR via an H2 O2 -dependent mechanism in squamous carcinoma cell line. Cancer Letters, 2010, 290: 43-48.