目的 檢測(cè)高遷移率族蛋白B1( HMGB1) 和α平滑肌肌動(dòng)蛋白( α-SMA) 在博萊霉素( BLM) 致小鼠肺纖維化模型肺內(nèi)的表達(dá)水平, 探討HMGB1 在肺纖維化發(fā)病機(jī)制中的作用。方法 取20 只4 ～6 周齡C57BL/6 雄性小鼠, 隨機(jī)分為BLM組和生理鹽水( NS) 對(duì)照組, 每組10 只。分別向氣管內(nèi)灌注BLM( 3 mg /kg) 和NS, 10 d 后處死小鼠。應(yīng)用RT-PCR 法檢測(cè)兩組肺組織HMGB1 和α-SMA的mRNA 表達(dá)水平, 應(yīng)用免疫組織化學(xué)檢測(cè)兩組肺組織中HMGB1 和α-SMA的蛋白表達(dá)水平。結(jié)果 RT-PCR 半定量和免疫組織化學(xué)半定量分析結(jié)果顯示, BLM組HMGB1 的mRNA 和蛋白表達(dá)均較NS 對(duì)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(dá)均較NS 對(duì)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(jié)論 在BLM誘導(dǎo)的肺纖維化中肺組織的HMGB1 和α-SMA 表達(dá)增加。肺纖維化病理過(guò)程可能與HMGB1 表達(dá)增加并活化α-SMA 的表達(dá)有關(guān)
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(dòng)蛋白在博萊霉素誘導(dǎo)肺纖維化中的表達(dá). 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2009, 09(2): 181-185. doi: 復(fù)制
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| 2. | 張敏, 徐軍. MAPKs 通路在轉(zhuǎn)化生長(zhǎng)因子β1 誘導(dǎo)氣道上皮細(xì)胞轉(zhuǎn)化中的作用. 中國(guó)呼吸與危重監(jiān)護(hù)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. 蔡琳, 吳壯, 徐軍. 博萊霉素誘導(dǎo)α平滑肌肌動(dòng)蛋白Cre 重組酶轉(zhuǎn)基因小鼠肺纖維化上皮細(xì)胞-間質(zhì)轉(zhuǎn)分化的研究. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2009, 8: 52-56.
- 2. 張敏, 徐軍. MAPKs 通路在轉(zhuǎn)化生長(zhǎng)因子β1 誘導(dǎo)氣道上皮細(xì)胞轉(zhuǎn)化中的作用. 中國(guó)呼吸與危重監(jiān)護(hù)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.