• 1 中國人民武裝警察部/ 隊后勤學(xué)院附屬醫(yī)院呼吸與重癥醫(yī)學(xué)科( 天津300162);;
  • 2 中國人民武裝警察部隊后勤學(xué)院附屬醫(yī)院心臟中心武警部隊心血管病研究所( 天津300162)通信作者: 魏路清, E-mail: luqing-wei@ 163. com#陳雪芬， 姬文婕為共同第一作者;

目的  探討博萊霉素誘導(dǎo)小鼠肺纖維化模型中, Krüppel 樣因子4( KLF4) 的表達及其意義。
方法  C57BL/6 小鼠隨機分為生理鹽水對照組( Control) 和博萊霉素組( BLM) , 經(jīng)氣管內(nèi)注入博萊霉素( 2. 5 mg/kg) 建立實驗性小鼠肺纖維化模型, 注入等量生理鹽水作為對照組, 分別于術(shù)后第12 h、1 d、2 d、3 d、7 d、14 d 及28 d 取材, 采用HE 染色和Masson 染色觀察肺組織病理變化及膠原的沉積部位和數(shù)量, 實時定量PCR 法和免疫組織化學(xué)法分別檢測各組肺組織中KLF4 mRNA 和蛋白表達水平。
結(jié)果  博萊霉素誘導(dǎo)的小鼠肺纖維化過程中, 第1、2 及3 d 表現(xiàn)為急性炎癥; 第7 d 炎癥加重, 并出現(xiàn)膠原沉積; 第14 d 肺泡結(jié)構(gòu)塌陷, 膠原沉積明顯; 第28 d 肺泡結(jié)構(gòu)基本正常, 炎癥程度和膠原沉積較輕。與對照組相比, 博萊霉素組小鼠肺組織中KLF4 mRNA 的表達水平第1 d 開始升高, 而后降低, 第3 d 達最低后逐漸升高直至第28 d。博萊霉素組小鼠肺組織中KLF4 蛋白的表達趨勢與mRNA 水平基本一致, 第1 d 開始升高, 而后降低, 第3 d 達最低后逐漸增加至第14 d 后再次降低。
結(jié)論  KLF4 在博萊霉素致肺纖維化過程中呈現(xiàn)明顯的動態(tài)變化, 并可能參與了肺纖維化的發(fā)生與發(fā)展。

引用本文： 陳雪芬 ,姬文婕,胡道川,馬永強,周欣,魏路清. Krüppel 樣因子4 在實驗性肺纖維化小鼠肺組織中的表達及意義. 中國呼吸與危重監(jiān)護雜志, 2013, 12(5): 509-512. doi: 復(fù)制

1. McConnell BB, Yang VW. Mammalian Kruppel-like factors in health and diseases. Physiol Rev, 2010, 90: 1337-1381.
2. Zhou Y, Hofstetter WL, He Y, et al. KLF4 inhibition of lung cancer cell invasion by suppression of SPARC expression. Cancer Biol Ther, 2010, 9: 507-513.
3. Liao X, Haldar SM, Lu Y, et al. Kruppel-like factor 4 regulates pressure-induced cardiac hypertrophy. J Mol Cell Cardiol, 2010 ,49: 334-338.
4. Rolipram attenuates bleomycin A5 -induced pulmonary fibrosis in rats. Respirology, 2009, 14: 975 -982.
5. Todd NW, Luzina IG, Atamas SP. Molecular and cellular mechanisms of pulmonary fibrosis. Fibrogenesis Tissue Repair,2012, 5: 11.
6. Artlett CM. Inflammasomes in wound healing and fibrosis. J Pathol, 2013, 229: 157-167 .
7. Hu B, Wu Z, Liu T, et al. Gut-enriched Kruppel-like factor interaction with Smad3 inhibits myofibroblast differentiation. Am J Respir Cell Mol Biol, 2007 , 36: 78-84.
8. Liu YN, Abou-Kheir W, Yin JJ, et al. Critical and reciprocal regulation of KLF4 and SLUG in transforming growth factor betainitiated prostate cancer epithelial-mesenchymal transition. Mol CellBiol, 2012 , 32: 941-953.
9. Feinberg MW, Cao Z, Wara AK, et al. Kruppel-like factor 4 is a mediator of proinflammatory signaling in macrophages. J Biol Chem, 2005, 280: 38247 -38258.
10. Duffield JS, Forbes SJ, Constandinou CM, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest, 2005, 115: 56-65.
11. Liao X, Sharma N, Kapadia F, et al. Kruppel-like factor 4 regulates macrophage polarization. J Clin Invest, 2011, 121: 2736-2749.
12. Alder JK, Georgantas RW, 3rd, Hildreth RL, et al. Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo. J Immunol, 2008, 180: 5645-5652.
13. Degryse AL, Lawson WE. Progress toward improving animal models for idiopathic pulmonary fibrosis. AmJ Med Sci, 2011,341: 444-449.
  1. 1. McConnell BB, Yang VW. Mammalian Kruppel-like factors in health and diseases. Physiol Rev, 2010, 90: 1337-1381.
  2. 2. Zhou Y, Hofstetter WL, He Y, et al. KLF4 inhibition of lung cancer cell invasion by suppression of SPARC expression. Cancer Biol Ther, 2010, 9: 507-513.
  3. 3. Liao X, Haldar SM, Lu Y, et al. Kruppel-like factor 4 regulates pressure-induced cardiac hypertrophy. J Mol Cell Cardiol, 2010 ,49: 334-338.
  4. 4. Rolipram attenuates bleomycin A5 -induced pulmonary fibrosis in rats. Respirology, 2009, 14: 975 -982.
  5. 5. Todd NW, Luzina IG, Atamas SP. Molecular and cellular mechanisms of pulmonary fibrosis. Fibrogenesis Tissue Repair,2012, 5: 11.
  6. 6. Artlett CM. Inflammasomes in wound healing and fibrosis. J Pathol, 2013, 229: 157-167 .
  7. 7. Hu B, Wu Z, Liu T, et al. Gut-enriched Kruppel-like factor interaction with Smad3 inhibits myofibroblast differentiation. Am J Respir Cell Mol Biol, 2007 , 36: 78-84.
  8. 8. Liu YN, Abou-Kheir W, Yin JJ, et al. Critical and reciprocal regulation of KLF4 and SLUG in transforming growth factor betainitiated prostate cancer epithelial-mesenchymal transition. Mol CellBiol, 2012 , 32: 941-953.
  9. 9. Feinberg MW, Cao Z, Wara AK, et al. Kruppel-like factor 4 is a mediator of proinflammatory signaling in macrophages. J Biol Chem, 2005, 280: 38247 -38258.
  10. 10. Duffield JS, Forbes SJ, Constandinou CM, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest, 2005, 115: 56-65.
  11. 11. Liao X, Sharma N, Kapadia F, et al. Kruppel-like factor 4 regulates macrophage polarization. J Clin Invest, 2011, 121: 2736-2749.
  12. 12. Alder JK, Georgantas RW, 3rd, Hildreth RL, et al. Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo. J Immunol, 2008, 180: 5645-5652.
  13. 13. Degryse AL, Lawson WE. Progress toward improving animal models for idiopathic pulmonary fibrosis. AmJ Med Sci, 2011,341: 444-449.

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