目的 探討在博萊霉素誘導(dǎo)的肺纖維化中是否發(fā)生了上皮細胞-間質(zhì)轉(zhuǎn)分化( EMT) 現(xiàn)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(zhuǎn)基因小鼠( α-SMA-Cre/R26R 雙轉(zhuǎn)基因鼠) 為實驗動物, 構(gòu)建博萊霉素誘導(dǎo)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(jié)果 氣管內(nèi)灌注博萊霉素的轉(zhuǎn)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(xiàn)或增多, 部分地區(qū)出現(xiàn)了支氣管周圍肺泡上皮細胞( ACE) 陽性藍染和浸潤。結(jié)論 在博萊霉素誘導(dǎo)的肺纖維化小鼠模型中可以觀察到EMT 現(xiàn)象, 氣道上皮細胞和肺泡上皮細胞能向間充質(zhì)細胞轉(zhuǎn)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(dǎo)α平滑肌肌動蛋白Cre 重組酶轉(zhuǎn)基因小鼠肺纖維化上皮細胞-間質(zhì)轉(zhuǎn)分化的研究. 中國呼吸與危重監(jiān)護雜志, 2009, 09(1): 52-56. doi: 復(fù)制
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| 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(zhuǎn)基因小鼠的建立. 軍事醫(yī)學(xué)科學(xué)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(zhuǎn)化生長因子β1 誘導(dǎo)氣道上皮細胞轉(zhuǎn)化中的作用. 中國呼吸與危重監(jiān)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(zhuǎn)基因小鼠的建立. 軍事醫(yī)學(xué)科學(xué)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(zhuǎn)化生長因子β1 誘導(dǎo)氣道上皮細胞轉(zhuǎn)化中的作用. 中國呼吸與危重監(jiān)護雜志, 2007, 6: 440-443.