格列衛對肺纖維化小鼠的干預機制_《中國呼吸與危重監護雜志》

作者：

李莉 ,  李燕芹

上海海交通大學醫學院附屬仁濟醫院呼吸科（上海 200127）;

關鍵詞：

格列衛肺纖維化博萊霉素 α-平滑肌肌動蛋白轉化生長因子

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目的探討格列衛對小鼠肺纖維化的干預機制。方法 120 只C57BL/6 小鼠隨機分為對照組、模型組、地塞米松組和格列衛組, 每組30 只。采用氣管內注射博萊霉素構建肺纖維化小鼠模型, 分別于7、14、21 d 隨機處死10 只動物。免疫組化檢測各組肺組織轉化生長因子β1 ( TGF-β1 )和α-平滑肌肌動蛋白( α-SMA) 的蛋白表達, RT-PCR 檢測肺組織TGF-β1 mRNA 含量。結果模型組各時間點TGF-β1 和α-SMA 的表達均較對照組顯著增加, 地塞米松和格列衛處理組各時間點TGF-β1和α-SMA 的表達均較模型組顯著降低, 而地塞米松組和格列衛組的表達水平無顯著差異。TGF-β1與α-SMA 表達水平呈直線正相關( r = 0. 251, P lt;0. 05) 。結論格列衛對博萊霉素誘導肺纖維化的抑制作用與其抑制TGF-β1 和α-SMA 的表達有關。

引用本文： 李莉 ,李燕芹. 格列衛對肺纖維化小鼠的干預機制. 中國呼吸與危重監護雜志, 2009, 09(4): 365-370. doi: 復制

1.	Davies HR, Richeldi L. Idiopathic pulmonary fibrosis: current and future treatment options. Am J Respir Med, 2002, 1: 211-224.
2.	American Thoracic Society. Idiopathic pulmonary fibrosis: Diagnosis and treatment international Consensus statement. Am J Respir Crit Care Med, 2000, 161: 646-664.
3.	Hoyles RK, Du Bois RM. Treatment of idiopathic pulmonary fibrosis: a European perspective Clin Pulm Med, 2006 , 13: 17-24.
4.	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.
5.	Dik WA, McAnulty RJ, Versnel MA, et al. Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats. Thorax, 2003, 58: 765-771.
6.	李莉, 李燕芹. 格列衛對博萊霉素致小鼠肺纖維化的干預作用.中國危重病急救醫學, 2007, 19: 229-232.
7.	Kolb M,Margetts PJ, Galt T, et al. Transient transgene expression of decorin in the lung reduces the fibrotic response to bleomycin. Am J Respir Crit Care Med, 2001, 163. : 770-777.
8.	李萬成, 劉維佳, 李艷萍, 等. 血管內皮生長因子受體抑制劑SU5416 對小鼠肺間質纖維化的影響. 中國呼吸與危重監護雜志, 2007, 6: 55-58.
9.	Aono Y, Nishioka Y, Inayama M, et al. Imatinib as a novel antifibrotic agent in bleomycin-induced pulmonary fibrosis in mice.Am J Respir Crit Care Med, 2005, 171: 1279-1285.
10.	陳碧, 張德平. 姜黃素干預對實驗性肺間質纖維化的影響. 中國呼吸與危重監護雜志, 2007, 6: 208-213.
11.	Torday JS, Torres E, Rehan VK. The role of fibroblast transdifferentiation in lung epithelial cell proliferation, differentiation and repair in vitro. Pediatr Pathol Mol Med, 2003, 22: 189-207.
12.	Untergasser G, Gander R, Lilg C, et al. Profiling molecular targets of TGF-β1 in prostate fibroblast- to-myofibroblast transdifferentiation.Mech Ageing Dev, 2005, 126: 59-69.
13.	穆茂, 程德云, 楊禮騰, 等. 阿魏酸鈉對肺纖維化大鼠肺組織轉化生長因子-β1 信號通路分子mRNA 表達的影響. 中國呼吸與危重監護雜志, 2007, 6: 110-113.
14.	黃山英, 宋良文. 效應細胞、細胞因子及相關基因調控在肺纖維化發生中的作用研究進展. 國外醫學呼吸系統分冊, 2005, 25:328-330.
15.	Shiwen X, Leask A, Denton CP, et al. Transforming growth factorbeta 1 induces endothelin expression by lung fibroblasts: possible role of endothelin in pulmonary fibrosis in scleroderma. BRITISH SOCIETY FOR RHEUMATOLOGY ANNUAL MEETING 19-22 APRIL 2005.
16.	Khalil N, Parekh TV, O’Connor R, et al. Regulation of the effects of TGF-beta 1 by activation of latent TGF-beta 1 and differential expression of TGF-beta receptors ( T beta R-I and T beta R-II) in idiopathic pulmonary fibrosis. Thorax, 2001 , 56 : 907-915.
17.	Phan SH. The myofibroblast in pulmonary fibrosis. Chest, 2002 ,122: 286s-289s.
18.	Zhang HY, Phan SHL. Inhibition of myofibroblast apoptosis by transforming growth factor beta. Am J Respir Cell Mol Biol, 1999 ,21: 658-665.
19.	Abdollahi A, Li M, Ping G, et al. Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis. J Exp Med,2005, 21, 201: 925-935.
20.	Supplement 1: i16, March 2005.

1. Davies HR, Richeldi L. Idiopathic pulmonary fibrosis: current and future treatment options. Am J Respir Med, 2002, 1: 211-224.
2. American Thoracic Society. Idiopathic pulmonary fibrosis: Diagnosis and treatment international Consensus statement. Am J Respir Crit Care Med, 2000, 161: 646-664.
3. Hoyles RK, Du Bois RM. Treatment of idiopathic pulmonary fibrosis: a European perspective Clin Pulm Med, 2006 , 13: 17-24.
4. 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.
5. Dik WA, McAnulty RJ, Versnel MA, et al. Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats. Thorax, 2003, 58: 765-771.
6. 李莉, 李燕芹. 格列衛對博萊霉素致小鼠肺纖維化的干預作用.中國危重病急救醫學, 2007, 19: 229-232.
7. Kolb M,Margetts PJ, Galt T, et al. Transient transgene expression of decorin in the lung reduces the fibrotic response to bleomycin. Am J Respir Crit Care Med, 2001, 163. : 770-777.
8. 李萬成, 劉維佳, 李艷萍, 等. 血管內皮生長因子受體抑制劑SU5416 對小鼠肺間質纖維化的影響. 中國呼吸與危重監護雜志, 2007, 6: 55-58.
9. Aono Y, Nishioka Y, Inayama M, et al. Imatinib as a novel antifibrotic agent in bleomycin-induced pulmonary fibrosis in mice.Am J Respir Crit Care Med, 2005, 171: 1279-1285.
10. 陳碧, 張德平. 姜黃素干預對實驗性肺間質纖維化的影響. 中國呼吸與危重監護雜志, 2007, 6: 208-213.
11. Torday JS, Torres E, Rehan VK. The role of fibroblast transdifferentiation in lung epithelial cell proliferation, differentiation and repair in vitro. Pediatr Pathol Mol Med, 2003, 22: 189-207.
12. Untergasser G, Gander R, Lilg C, et al. Profiling molecular targets of TGF-β1 in prostate fibroblast- to-myofibroblast transdifferentiation.Mech Ageing Dev, 2005, 126: 59-69.
13. 穆茂, 程德云, 楊禮騰, 等. 阿魏酸鈉對肺纖維化大鼠肺組織轉化生長因子-β1 信號通路分子mRNA 表達的影響. 中國呼吸與危重監護雜志, 2007, 6: 110-113.
14. 黃山英, 宋良文. 效應細胞、細胞因子及相關基因調控在肺纖維化發生中的作用研究進展. 國外醫學呼吸系統分冊, 2005, 25:328-330.
15. Shiwen X, Leask A, Denton CP, et al. Transforming growth factorbeta 1 induces endothelin expression by lung fibroblasts: possible role of endothelin in pulmonary fibrosis in scleroderma. BRITISH SOCIETY FOR RHEUMATOLOGY ANNUAL MEETING 19-22 APRIL 2005.
16. Khalil N, Parekh TV, O’Connor R, et al. Regulation of the effects of TGF-beta 1 by activation of latent TGF-beta 1 and differential expression of TGF-beta receptors ( T beta R-I and T beta R-II) in idiopathic pulmonary fibrosis. Thorax, 2001 , 56 : 907-915.
17. Phan SH. The myofibroblast in pulmonary fibrosis. Chest, 2002 ,122: 286s-289s.
18. Zhang HY, Phan SHL. Inhibition of myofibroblast apoptosis by transforming growth factor beta. Am J Respir Cell Mol Biol, 1999 ,21: 658-665.
19. Abdollahi A, Li M, Ping G, et al. Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis. J Exp Med,2005, 21, 201: 925-935.
20. Supplement 1: i16, March 2005.

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格列衛對肺纖維化小鼠的干預機制

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