目的 比較兩種表皮生長(zhǎng)因子受體酪氨酸激酶抑制劑( EGFR-TKI) 吉非替尼與厄羅替尼對(duì)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(duì)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(shí)驗(yàn)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(shí), 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(cè)總EGFR 及磷酸化EGFR; 右肺勻漿檢測(cè)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(wú)明顯差異( P gt;0. 05) 。結(jié)論 EGFR-TKI 通過(guò)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(zhǎng)因子受體酪氨酸激酶抑制劑對(duì)小鼠肺纖維化的干預(yù)作用比較. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(4): 426-429. doi: 復(fù)制
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| 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(yáng), 車東媛, 等. 肺纖維化大鼠肺內(nèi)血小板源生長(zhǎng)因子受體的表達(dá)及黃芪對(duì)其的影響. 同濟(jì)醫(yī)科大學(xué)學(xué)報(bào), 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. |
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- 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(yáng), 車東媛, 等. 肺纖維化大鼠肺內(nèi)血小板源生長(zhǎng)因子受體的表達(dá)及黃芪對(duì)其的影響. 同濟(jì)醫(yī)科大學(xué)學(xué)報(bào), 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.