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_《中國呼吸與危重監護雜志》

作者：

蔡琳 ¹ , 李理 ² ,  徐軍 ¹

1 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）;;
2 廣州軍區廣州總醫院呼吸內科（廣東廣州 510010）;

關鍵詞：

肺纖維化博萊霉素高遷移率族蛋白B1 α平滑肌肌動蛋白發病機制

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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. 中國呼吸與危重監護雜志, 2009, 09(2): 181-185. doi: 復制

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. 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, 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.

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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

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《中國呼吸與危重監護雜志》

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

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