蔡琳 1 , 李理 2 , 徐軍 1
  • 1 廣州醫(yī)學院第一附屬醫(yī)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）;;
  • 2 廣州軍區(qū)廣州總醫(yī)院呼吸內科（廣東廣州 510010）;

目的  檢測高遷移率族蛋白B1( HMGB1) 和α平滑肌肌動蛋白( α-SMA) 在博萊霉素( BLM) 致小鼠肺纖維化模型肺內的表達水平, 探討HMGB1 在肺纖維化發(fā)病機制中的作用。方法  取20 只4 ～6 周齡C57BL/6 雄性小鼠, 隨機分為BLM組和生理鹽水( NS) 對照組, 每組10 只。分別向氣管內灌注BLM( 3 mg /kg) 和NS, 10 d 后處死小鼠。應用RT-PCR 法檢測兩組肺組織HMGB1 和α-SMA的mRNA 表達水平, 應用免疫組織化學檢測兩組肺組織中HMGB1 和α-SMA的蛋白表達水平。結果  RT-PCR 半定量和免疫組織化學半定量分析結果顯示, BLM組HMGB1 的mRNA 和蛋白表達均較NS 對照組顯著增加( 0. 61 ±0. 08 比0. 15 ±0. 02, 13. 12 ±1. 33 比7. 92 ±1. 10, P 均 lt;0. 01) ; BLM組α-SMA 的mRNA 和蛋白表達均較NS 對照組顯著增加( 0. 89 ±0. 12 比0. 60 ±0. 07,13. 66 ±1. 01 比8. 18 ±1. 33, P 均 lt;0. 01) 。結論  在BLM誘導的肺纖維化中肺組織的HMGB1 和α-SMA 表達增加。肺纖維化病理過程可能與HMGB1 表達增加并活化α-SMA 的表達有關

引用本文： 蔡琳,李理,徐軍. 高遷移率族蛋白B1 和α平滑肌肌動蛋白在博萊霉素誘導肺纖維化中的表達. 中國呼吸與危重監(jiān)護雜志, 2009, 09(2): 181-185. doi: 復制

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1. 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(jiān)護雜志, 2009, 8: 52-56.
2. 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(jiān)護雜志, 2007, 6: 440-443.
3. Phan SH. The myofibroblast in pulmonary fibrosis. Chest, 2002 ,122: 286s-289s.
4. Sadikot RT, Christman JW, Blackwell TS. Molecular targets for modulating lung inflammation and injury. Curr Drug Targets, 2004 ,5: 581-588.
5. White ES, Atrasz RG, Hu B, et al. Negative regulation of myofibroblast differentiation by PTEN ( Phosphatase and Tensin Homolog Deleted on chromosome 10 ) . AmJ Respir Crit Care Med,2006, 173: 112-121.
6. Lotze MT, Tracey KJ. High-mobility group box 1 protein( HMGB1) :nuclear weapon in the immune arsenal. Nat Rev Immunol, 2005, 5 :331-342.
7. Bustin M. Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins. Mol Cell Biol, 1999, 19 : 5237 -5246 .
8. 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.
9. Schissel SL, Layne MD. Telomerase, myofibroblasts, and pulmonary fibrosis. Am J Respir Cell Mol Biol, 2006, 34: 520-522.
10. Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med, 2001, 345: 517-525.
11. Zhang HY, Gharaee-Kermani M, Zhang K, et al. Lung fibroblast alpha-smooth muscle actin expression and contractile phenotype in bleomycin-induced pulmonary fibrosis. Am JPathol, 1996, 148: 527-537.
12. Darby I, Skalli O, Gabbiani G. Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest, 1990, 63: 21-29.
13. Goodwin GH, Sanders C, Johns EW. A new group of chromatinassociated proteins with a high content of acidic and basic amino acids. Eur J Biochem, 1973, 38: 14-19.
14. Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature, 2002 , 418 :191-195.
15. Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science, 1999, 285: 248-251.
16. Yang H, Ochani J, Li J, et al. Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA, 2004, 101: 296-301.
17. Andersson U, Wang H, Palmblad K, et al. High mobility group 1 protein( HMG-1 ) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med, 2000, 192: 565-570.
18. He M, Kubo H, Ishizawa K, et al. The role of the receptor for advanced glycation end-products in lung fibrosis. AmJ Physiol Lung Cell Mol Physiol, 2007, 293: L1427-L1436.
  1. 1. 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(jiān)護雜志, 2009, 8: 52-56.
  2. 2. 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(jiān)護雜志, 2007, 6: 440-443.
  3. 3. Phan SH. The myofibroblast in pulmonary fibrosis. Chest, 2002 ,122: 286s-289s.
  4. 4. Sadikot RT, Christman JW, Blackwell TS. Molecular targets for modulating lung inflammation and injury. Curr Drug Targets, 2004 ,5: 581-588.
  5. 5. White ES, Atrasz RG, Hu B, et al. Negative regulation of myofibroblast differentiation by PTEN ( Phosphatase and Tensin Homolog Deleted on chromosome 10 ) . AmJ Respir Crit Care Med,2006, 173: 112-121.
  6. 6. Lotze MT, Tracey KJ. High-mobility group box 1 protein( HMGB1) :nuclear weapon in the immune arsenal. Nat Rev Immunol, 2005, 5 :331-342.
  7. 7. Bustin M. Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins. Mol Cell Biol, 1999, 19 : 5237 -5246 .
  8. 8. 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.
  9. 9. Schissel SL, Layne MD. Telomerase, myofibroblasts, and pulmonary fibrosis. Am J Respir Cell Mol Biol, 2006, 34: 520-522.
  10. 10. Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med, 2001, 345: 517-525.
  11. 11. Zhang HY, Gharaee-Kermani M, Zhang K, et al. Lung fibroblast alpha-smooth muscle actin expression and contractile phenotype in bleomycin-induced pulmonary fibrosis. Am JPathol, 1996, 148: 527-537.
  12. 12. Darby I, Skalli O, Gabbiani G. Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest, 1990, 63: 21-29.
  13. 13. Goodwin GH, Sanders C, Johns EW. A new group of chromatinassociated proteins with a high content of acidic and basic amino acids. Eur J Biochem, 1973, 38: 14-19.
  14. 14. Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature, 2002 , 418 :191-195.
  15. 15. Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science, 1999, 285: 248-251.
  16. 16. Yang H, Ochani J, Li J, et al. Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA, 2004, 101: 296-301.
  17. 17. Andersson U, Wang H, Palmblad K, et al. High mobility group 1 protein( HMG-1 ) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med, 2000, 192: 565-570.
  18. 18. He M, Kubo H, Ishizawa K, et al. The role of the receptor for advanced glycation end-products in lung fibrosis. AmJ Physiol Lung Cell Mol Physiol, 2007, 293: L1427-L1436.

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