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作用比較_《中國呼吸與危重監護雜志》

作者：

李偉峰 ¹ , 李理 ¹ , 袁偉鋒 ^1,2 , 徐虹 ¹ , 黃文杰 ¹

1 廣州軍區廣州總醫院呼吸內科( 廣東廣州510010) ;;
2 南方醫科大學研究生學院( 廣東廣州510515)通訊作者: 李理, E-mail: lili_china@ 163. com;

關鍵詞：

表皮生長因子受體酪氨酸激酶抑制劑厄羅替尼吉非替尼肺纖維化博萊霉素

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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 組小鼠經氣管滴入博萊霉素致肺纖維化, NS 組氣管內滴入生理鹽水; 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構破壞、膠原沉積, 降低磷酸化EGFR 表達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) 。結論 EGFR-TKI 通過抑制EGFR 磷酸化, 有效減輕博萊霉素誘導的肺纖維化形成, 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作用比較. 中國呼吸與危重監護雜志, 2010, 9(4): 426-429. doi: 復制

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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, 車東媛, 等. 肺纖維化大鼠肺內血小板源生長因子受體的表達及黃芪對其的影響. 同濟醫科大學學報, 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.

《中國呼吸與危重監護雜志》

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作用比較

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《中國呼吸與危重監護雜志》

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作用比較

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料