• 1 解放軍空軍總醫(yī)院呼吸內(nèi)科（北京市 100036）;;
  • 2 北京宣武醫(yī)院神經(jīng)疾病研究所;

目的 研究細(xì)胞因子[白細(xì)胞介素-4（IL-4），腫瘤壞死因子-α（TNF-α）]和支氣管哮喘治療藥物（地塞米松，氨茶堿，沙丁胺醇）對(duì)氣管上皮細(xì)胞內(nèi)組胺N-甲基轉(zhuǎn)移酶（HMT）活性的影響。方法 培養(yǎng)永生化人支氣管上皮細(xì)胞株BEAS-2B細(xì)胞，至細(xì)胞接近融合時(shí)分別加入不同濃度的TNF-α、IL-4、地塞米松、沙丁胺醇和氨茶堿培養(yǎng)24 h后，用高效液相色譜法檢測(cè)細(xì)胞內(nèi)HMT的活性。結(jié)果 氣管上皮細(xì)胞內(nèi)HMT的活性為（50±7）pmol?min-1?mg pro-1。TNF-α和IL-4分別在1 ng/mL和5 ng/mL及以上濃度時(shí)明顯減低HMT的活性，10 ng/mL時(shí)達(dá)到最大抑制效果。地塞米松和氨茶堿可明顯抑制TNF-α所致HMT活性的降低，沙丁胺醇則無(wú)明顯抑制作用。結(jié)論 IL-4和TNF-α導(dǎo)致的HMT活性降低，可能是氣道高反應(yīng)性的重要原因之一；糖皮質(zhì)激素和茶堿類藥物抑制TNF-α所致的HMT活性降低可能是其治療哮喘的又一作用機(jī)制。

引用本文： 劉一,張波,李堯華,紀(jì)樹(shù)國(guó). 氣管上皮細(xì)胞內(nèi)組胺N-甲基轉(zhuǎn)移酶活性調(diào)節(jié)的實(shí)驗(yàn)研究. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2007, 6(1): 19-22. doi: 復(fù)制

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2. Sekizawa K，Nakazawa H，Ohrui T，et al.Histamine N-methyltransferase modulates histamine- and antigen-induced bronchoconstriction in guinea pigs in vivo.Am Rev Respir Dis，1993，147：92-96.
3. Nakazawa H，Sekizawa K，Morikawa M，et al.Viral respiratory infection causes airway hyperresponsive and decreases histamine N-methyltransferase activity in guinea pigs.Am J Respir Crit Care Med，1994，29：180-185.
4. Hoshi H，Yamauchi K，Sekizawa K，et al.Nitrogen dioxide exposure increases airway contractile response to histamine by decreasing histamine N-methyltransferase activity in guinea pigs.Am J Respir Cell Mol Biol，1996，14：76-83.
5. Tamaoki J，Araake M，Chiyotani A，et al.Airway hyperresponsiveness to histamine in mycoplasmal infection：role of histamine N-methyltransferase.Eur J Pharmacol，1998，247：257-260.
6. Fukuda H，Yamatodani A，Imamura I，et al.High-performance liquid chromatographic determination of histamine N-methyltransferase activity.J Chromatography，1991，567：459-464.
7. Lowry OH，Rosebrough NJ，F(xiàn)arr AL，et al.Protein measurement with the Folin phenol reagent.J Biol Chem，1951，193：265-275.
8. Bryce PJ，Mathias CB，Harrison KL，et al.The H1 histamine receptor regulates allergic lung responses.J Clin Invest，2006，116：1624-1632.
9. Yan L，Galinsky RE，Bernstein JA，et al.Histamine N-methyltransferase pharmacogenetics：association of a common functional polymorphism with asthma.Pharmacogenetics，2000，10：261-266.
10. 湯葳，陳雪華，張奕，等.支氣管上皮細(xì)胞IL-6和IL-8的研究.上海第二醫(yī)科大學(xué)學(xué)報(bào)，2005，25：694-697.
11. Wheeler AP，Jesmok G，Brigham KL.Tumor necrosis factor’s effects on lung mechanics，gas exchange，and airway reactivity in sheep.J Appl Physiol，1990，68：2542-2549.
12. To Y，Dohi M，Tanaka R，et al.Early interleukin 4-dependent response can induce airway hyperreactivity before development of airway inflammation in a mouse model of asthma.Lab Invest，2001，81：1385-1396.
13. Barnes PJ，Pedersen S.Efficacy and safety of inhaled corticosteroids in asthma.Report of a workshop held in Eze，F(xiàn)rance，October 1992.Am Rev Respir Dis，1993，148：S1-S26.
14. Barnes PJ，Adcock I.Anti-inflammatory actions of steroids：molecular mechanisms.Trends Pharmacol Sci，1993，14：436-441.
15. Finnerty JP，Lee C，Willson S，et al.Effects of theophylline on inflammatory cells and cytokines in asthmatic subjects.Eur Respir J，1996，9：1672-1677.
16. 曾艷，郭華民，劉丹，等.經(jīng)氨茶堿治療后哮喘大鼠血TNF-α及肺病理改變.小兒急救醫(yī)學(xué)，1998，5：157-159.
17. Tomita K，Chikuni H，Tokuyasu H，et al.Functional assay of NF-κB translocation into nuclei by laser scanning cytometry：inhibitory effect by dexamethasone or theophylline.Naumyn Schmiedebergs Arch Oharmacol，1999，359：249-255.
  1. 1. Yamauchi K，Sekizawa K，Suzuli H，et al.Structure and function of human histamine N-methyltransferase：critical enzyme in histamine metabolism in airway.Am J Physiol，1994，267：L342-L349.
  2. 2. Sekizawa K，Nakazawa H，Ohrui T，et al.Histamine N-methyltransferase modulates histamine- and antigen-induced bronchoconstriction in guinea pigs in vivo.Am Rev Respir Dis，1993，147：92-96.
  3. 3. Nakazawa H，Sekizawa K，Morikawa M，et al.Viral respiratory infection causes airway hyperresponsive and decreases histamine N-methyltransferase activity in guinea pigs.Am J Respir Crit Care Med，1994，29：180-185.
  4. 4. Hoshi H，Yamauchi K，Sekizawa K，et al.Nitrogen dioxide exposure increases airway contractile response to histamine by decreasing histamine N-methyltransferase activity in guinea pigs.Am J Respir Cell Mol Biol，1996，14：76-83.
  5. 5. Tamaoki J，Araake M，Chiyotani A，et al.Airway hyperresponsiveness to histamine in mycoplasmal infection：role of histamine N-methyltransferase.Eur J Pharmacol，1998，247：257-260.
  6. 6. Fukuda H，Yamatodani A，Imamura I，et al.High-performance liquid chromatographic determination of histamine N-methyltransferase activity.J Chromatography，1991，567：459-464.
  7. 7. Lowry OH，Rosebrough NJ，F(xiàn)arr AL，et al.Protein measurement with the Folin phenol reagent.J Biol Chem，1951，193：265-275.
  8. 8. Bryce PJ，Mathias CB，Harrison KL，et al.The H1 histamine receptor regulates allergic lung responses.J Clin Invest，2006，116：1624-1632.
  9. 9. Yan L，Galinsky RE，Bernstein JA，et al.Histamine N-methyltransferase pharmacogenetics：association of a common functional polymorphism with asthma.Pharmacogenetics，2000，10：261-266.
  10. 10. 湯葳，陳雪華，張奕，等.支氣管上皮細(xì)胞IL-6和IL-8的研究.上海第二醫(yī)科大學(xué)學(xué)報(bào)，2005，25：694-697.
  11. 11. Wheeler AP，Jesmok G，Brigham KL.Tumor necrosis factor’s effects on lung mechanics，gas exchange，and airway reactivity in sheep.J Appl Physiol，1990，68：2542-2549.
  12. 12. To Y，Dohi M，Tanaka R，et al.Early interleukin 4-dependent response can induce airway hyperreactivity before development of airway inflammation in a mouse model of asthma.Lab Invest，2001，81：1385-1396.
  13. 13. Barnes PJ，Pedersen S.Efficacy and safety of inhaled corticosteroids in asthma.Report of a workshop held in Eze，F(xiàn)rance，October 1992.Am Rev Respir Dis，1993，148：S1-S26.
  14. 14. Barnes PJ，Adcock I.Anti-inflammatory actions of steroids：molecular mechanisms.Trends Pharmacol Sci，1993，14：436-441.
  15. 15. Finnerty JP，Lee C，Willson S，et al.Effects of theophylline on inflammatory cells and cytokines in asthmatic subjects.Eur Respir J，1996，9：1672-1677.
  16. 16. 曾艷，郭華民，劉丹，等.經(jīng)氨茶堿治療后哮喘大鼠血TNF-α及肺病理改變.小兒急救醫(yī)學(xué)，1998，5：157-159.
  17. 17. Tomita K，Chikuni H，Tokuyasu H，et al.Functional assay of NF-κB translocation into nuclei by laser scanning cytometry：inhibitory effect by dexamethasone or theophylline.Naumyn Schmiedebergs Arch Oharmacol，1999，359：249-255.