博萊霉素誘導α平滑肌肌動蛋白Cre 重組酶轉基因小鼠肺纖維化上皮細胞-間質轉分化的研究_《中國呼吸與危重監護雜志》

作者：

蔡琳 , 吳壯 , 徐軍

廣州醫學院第一附屬醫院廣州呼吸疾病研究所呼吸疾病國家重點實驗室（廣東廣州 510120）;

關鍵詞：

上皮細胞-間質轉分化肺纖維化博萊霉素 Cre重組酶 α平滑肌肌動蛋白轉基因小鼠

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目的探討在博萊霉素誘導的肺纖維化中是否發生了上皮細胞-間質轉分化( EMT) 現象, 支氣管上皮細胞是否參與了這一過程。方法采用α平滑肌肌動蛋白Cre 重組酶轉基因小鼠( α-SMA-Cre/R26R 雙轉基因鼠) 為實驗動物, 構建博萊霉素誘導的小鼠肺纖維化模型, 進行組織X-gal 染色和α平滑肌肌動蛋白免疫熒光檢測。結果氣管內灌注博萊霉素的轉基因小鼠支氣管上皮下部分X-gal 藍染明顯增多, 終末小氣道周圍和肺血管壁藍染細胞出現或增多, 部分地區出現了支氣管周圍肺泡上皮細胞( ACE) 陽性藍染和浸潤。結論在博萊霉素誘導的肺纖維化小鼠模型中可以觀察到EMT 現象, 氣道上皮細胞和肺泡上皮細胞能向間充質細胞轉化, 參與肺纖維化病理過程。

引用本文： 蔡琳,吳壯,徐軍. 博萊霉素誘導α平滑肌肌動蛋白Cre 重組酶轉基因小鼠肺纖維化上皮細胞-間質轉分化的研究. 中國呼吸與危重監護雜志, 2009, 09(1): 52-56. doi: 復制

1.	Kuhn C, McDonald JA. The roles of the myofibroblast in idiopathic pulmonary fibrosis. Ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis. Am J Pathol, 1991 ,138: 1257-1265.
2.	Schissel SL, Layne MD. Telomerase, myofibroblasts, and pulmonary fibrosis. Am J Respir Cell Mol Biol, 2006, 34: 520-522.
3.	White ES, Atrasz RG, Hu B, et al. Negative regulation of myofibroblast differentiation by PTEN ( Phosphatase and Tensin Homolog Deleted on chromosome 10. Am J Respir Crit Care Med, 2006, 173 :112 -121.
4.	Kasai H, Allen JT, Mason RM, et al. TGF-betal induces human alveolar epithelial to mesenchymal cell transition ( EMT) . Respir Res,2005, 6: 56.
5.	Hamilton DL, Abremski K. Site-specific recombination by the bacteriophage P1 lox-Cre system. Cre-mediated synapsis of two lox sites. J Mol Biol, 1984, 178: 481-486.
6.	Willis BC, Liebler JM, Luby-Phelps K, et al. Induction of epithelialmesenchymal transition in alveolar epithelial cells by transforming growth factor-betal: potential role in idiopathic pulmonary fibrosis.Am J Pathol, 2005, 166: 1321-1332.
7.	Yao HW, Xie QM, Chen JQ, et al. TGF-beta induces alveolar epithelial to mesenchymal transition in vitro. Life Sci, 2004, 76: 29-37.
8.	楊蕾蕾, 吳壯, 程萱, 等. 平滑肌細胞特異表達Cre 重組酶轉基因小鼠的建立. 軍事醫學科學院院刊, 2005, 29: 219-222.
9.	Kim KK, Kugler MC, Wolters PJ, et al. Alveolar epithelial cellmesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA, 2006 ,103: 13180-13185.
10.	Metzger D, Clifford J, Chiba H, et al. Conditional site-specific recombination in mammalian cells using a liganddependent chimeric Cre recombinase. Proc Natl Acad Sci USA, 1995, 92: 6991-6995.
11.	Grinnell F, Ho CH. Transforming growth factor beta stimulates fibroblast-collagen matrix contraction by different mechanisms in mechanically loaded and unloaded matrices. Exp Cell Res, 2002, 273 :248 -255.
12.	Borzone G, Moreno R, Urrea R, et al. Bleomycin-induced chroniclung damage does not resemble human idiopathic pulmonary fibrosis.Am J Respir Crit Care Med, 2001, 163: 1648-1653.
13.	張敏, 徐軍. MAPKs 通路在轉化生長因子β1 誘導氣道上皮細胞轉化中的作用. 中國呼吸與危重監護雜志, 2007, 6: 440-443.

1. Kuhn C, McDonald JA. The roles of the myofibroblast in idiopathic pulmonary fibrosis. Ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis. Am J Pathol, 1991 ,138: 1257-1265.
2. Schissel SL, Layne MD. Telomerase, myofibroblasts, and pulmonary fibrosis. Am J Respir Cell Mol Biol, 2006, 34: 520-522.
3. White ES, Atrasz RG, Hu B, et al. Negative regulation of myofibroblast differentiation by PTEN ( Phosphatase and Tensin Homolog Deleted on chromosome 10. Am J Respir Crit Care Med, 2006, 173 :112 -121.
4. Kasai H, Allen JT, Mason RM, et al. TGF-betal induces human alveolar epithelial to mesenchymal cell transition ( EMT) . Respir Res,2005, 6: 56.
5. Hamilton DL, Abremski K. Site-specific recombination by the bacteriophage P1 lox-Cre system. Cre-mediated synapsis of two lox sites. J Mol Biol, 1984, 178: 481-486.
6. Willis BC, Liebler JM, Luby-Phelps K, et al. Induction of epithelialmesenchymal transition in alveolar epithelial cells by transforming growth factor-betal: potential role in idiopathic pulmonary fibrosis.Am J Pathol, 2005, 166: 1321-1332.
7. Yao HW, Xie QM, Chen JQ, et al. TGF-beta induces alveolar epithelial to mesenchymal transition in vitro. Life Sci, 2004, 76: 29-37.
8. 楊蕾蕾, 吳壯, 程萱, 等. 平滑肌細胞特異表達Cre 重組酶轉基因小鼠的建立. 軍事醫學科學院院刊, 2005, 29: 219-222.
9. Kim KK, Kugler MC, Wolters PJ, et al. Alveolar epithelial cellmesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA, 2006 ,103: 13180-13185.
10. Metzger D, Clifford J, Chiba H, et al. Conditional site-specific recombination in mammalian cells using a liganddependent chimeric Cre recombinase. Proc Natl Acad Sci USA, 1995, 92: 6991-6995.
11. Grinnell F, Ho CH. Transforming growth factor beta stimulates fibroblast-collagen matrix contraction by different mechanisms in mechanically loaded and unloaded matrices. Exp Cell Res, 2002, 273 :248 -255.
12. Borzone G, Moreno R, Urrea R, et al. Bleomycin-induced chroniclung damage does not resemble human idiopathic pulmonary fibrosis.Am J Respir Crit Care Med, 2001, 163: 1648-1653.
13. 張敏, 徐軍. MAPKs 通路在轉化生長因子β1 誘導氣道上皮細胞轉化中的作用. 中國呼吸與危重監護雜志, 2007, 6: 440-443.

《中國呼吸與危重監護雜志》

博萊霉素誘導α平滑肌肌動蛋白Cre 重組酶轉基因小鼠肺纖維化上皮細胞-間質轉分化的研究

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《中國呼吸與危重監護雜志》

博萊霉素誘導α平滑肌肌動蛋白Cre 重組酶轉基因小鼠肺纖維化上皮細胞-間質轉分化的研究

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