• 中南大學湘雅醫(yī)院呼吸科（湖南長沙 410008）;

目的  探討呼吸道合胞病毒( RSV) 感染SD 大鼠肺內(nèi)神經(jīng)營養(yǎng)因子水平的變化, 及其與氣道神經(jīng)可塑性改變和氣道高反應性間的關(guān)系。方法  1 ～2 周齡SD 幼鼠共20 只, 隨機分為正常對照組和RSV 感染組, 每組10 只。RSV 感染組采用每周1 次RSV 滴鼻法制作RSV 感染模型。第8周進行氣道阻力測定, 留取左肺行HE 染色觀察肺部病理學變化, 免疫組織化學染色檢測氣道突觸囊泡素( SYN) 和神經(jīng)絲( NF) 的表達, 原位雜交法檢測肺組織RSV RNA。ELISA 法檢測肺組織中神經(jīng)營養(yǎng)因子[ 神經(jīng)生長因子( NGF) 、腦源性神經(jīng)營養(yǎng)因子( BDNF) 、神經(jīng)營養(yǎng)因子3( NT3) 及神經(jīng)營養(yǎng)因子4( NT4) ] 水平。結(jié)果  RSV 感染組大鼠肺組織內(nèi)可見大量炎癥細胞浸潤, 原位雜交顯示肺間質(zhì)細胞中有明顯的RSV RNA 陽性信號, 表明模型建立成功。RSV 感染組氣道反應性顯著增高, 氣道感覺神經(jīng)元SYN 及NF 的表達顯著增高, 肺部NGF 及BDNF 水平較對照組明顯增高( P  lt;0. 05) , 而NT3 及NT4 水平與對照組無顯著差異( P  gt; 0. 05) 。NGF 及BDNF 濃度與氣道SYN 表達呈正相關(guān)( r1 =0. 892, r2 =0. 995, P  lt;0. 05) , 與NF表達呈正相關(guān)( r1 =0. 949, r2 = 0. 936, P  lt; 0. 05) , 與氣道反應性也呈正相關(guān)( r1 = 0. 929, r2 =0. 910, P  lt;0. 05) 。結(jié)論  RSV 感染后肺部NGF、BDNF 水平增高, 并與氣道神經(jīng)可塑性變化和氣道高反應性密切相關(guān)

引用本文： 趙然然,潘頻華,覃慶武,王慧,胡成平. 呼吸道合胞病毒感染大鼠氣道神經(jīng)營養(yǎng)因子水平與氣道神經(jīng)可塑性研究. 中國呼吸與危重監(jiān)護雜志, 2009, 09(2): 141-145. doi: 復制

1. Ogra PL. Respiratory syncytial virus: The virus, the disease and the immune reponse. Paediatr Respir Rev, 2004, 5( suppl A) : S119-S126.
2. Gern JE. Mechanisms of virus-induced asthma. J Pediatr, 2003, 142 ( suppl 2) : S9-S13.
3. Johnston SL, Pattenmore PK, Sanderson G, et a1. The relationship between upper respiratory infections and hospital admissionss for asthma: a time-trend anylysis. Am J Respir Crit Care Med, 1996 ,154( 3 Pt 1) : 654-660.
4. KerzelS,P　uth G, Nockher WA, et al. Pan-neurotrophin receptor p75 contributes to neuronal hyperreactivity and airway inflammation in a murine model of experimental asthma. Am J Respir Cell Mol Biol, 2003, 28: 170-178.
5. Ruuskanen O, Ogra PL. Respiratory syncytial virus. Curr Probl Pediatr, 1993, 23: 50-79.
6. Shen XY, Pan PH, Wu ES, et al. Effects of respiratory syncytial virus infection on the airway neuronal plasticity and its relationship to the bronchial hyperresponsiveness in rats. Chin Med J( Engl) ,2006, 119: 156-159.
7. Hu CB, Wedde-Beer K, Auais A, et al. Nerve growth factor and nerve growth factor receptors in respiratory syncytial virus-infected lungs. Am J Physiol Lung Cell Mol physiol, 2002, 283: L494-L502.
8. Hamelmann E, Schwarze J, Takeda K, et al. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med, 1997 ,156: 766-775.
9. 沈丹華, 廖曉耘, 劉艷麗, 等. 胎盤部位過度反應及胎盤部位結(jié)節(jié)的臨床病理分析, 中華病理學雜志, 2004, 33: 441-444.
10. Simoes EA. Respiratory syncytial virus infection. Lancet, 1999, 354 :847-852.
11. Sigurs N, Gustafsson PM, Bjarnason R, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med, 2005, 171: 137-141.
12. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci, 2001, 24: 677-736.
13. Delcroix JD, Valletta J, Wu C, et al. Trafficking the NGF signal:implications for normal and degenerating neurons. Prog Brain Res,2004, 146: 3-23.
14. Huang EJ, Wilkinson GA, Fari　as I, et al. Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo evidence for NT-3 activation of TrkA and TrkB in addition to TrkC.Development, 1999, 126: 2191-2203.
15. Ringstedt T, Ib　　ez CF, Nosrat CA. Role of brain-derived neurotrophic factor in target invasion in the gustatory system. J Neurosci, 1999, 19: 3507-3518.
16. Piedimonle G. Contribution of neuroimmune mechanisms to airway inflammation and remodeling during and after respiratory syncytial virus infection. Pediatr Infect Dis J, 2003, 22: S66-S75.
17. Tortorolo L, Langer A, Polidori G, et al. Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection. Am J Respir Crit Care Med, 2005, 172: 233-237.
18. Hoffman PN. Distinct Roles of Neurofilament and Tubulin Gene Expression in Axonal Growth. Ciba Found Symp, 1988,138: 192-204.
19. de Vries A, van Rijnsoever C, Engels F, et al. The role of sensory nerve endings in nerve growth factor-induced airway hyperresponsiveness to histamine in guinea-pigs. Br J Pharmacol, 2001 , 134 :771-776.
20. de Vries A, Dessing MC, Engels F, et al. Nerve growth factor induces a neurokinin-1 receptor-mediated airway hyperrespon-siveness in guinea pigs. Am J Respir Crit Care Med, 1999, 159: 1541-1544.
21. Friberg SG, Olgart H　glund C, Gustafsson LE. Nerve growth factor increase airway responssives and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea pig model.Acta Physiol Scand, 2001, 173: 239-245.
22. Ann NY. Neurotrophins in Allergic Airway Dysfunction What the Mouse Model Is Teching Us. Acad Sci, 2003, 992: 241-249.
23. 潘頻華, 王慧, 胡成平. 呼吸道合胞病毒感染大鼠脊髓背根節(jié)突觸囊泡素的表達與氣道反應性的關(guān)系. 中國呼吸與危重監(jiān)護雜志, 2007, 6: 294-297.
24. Randolph CL, Bierl MA, Isaacson LG. Regulation of NGF and NT3 protein expression in peripheral targets by sympathetic input. Brain Res, 2007, 1144: 59-69.
  1. 1. Ogra PL. Respiratory syncytial virus: The virus, the disease and the immune reponse. Paediatr Respir Rev, 2004, 5( suppl A) : S119-S126.
  2. 2. Gern JE. Mechanisms of virus-induced asthma. J Pediatr, 2003, 142 ( suppl 2) : S9-S13.
  3. 3. Johnston SL, Pattenmore PK, Sanderson G, et a1. The relationship between upper respiratory infections and hospital admissionss for asthma: a time-trend anylysis. Am J Respir Crit Care Med, 1996 ,154( 3 Pt 1) : 654-660.
  4. 4. KerzelS,P　uth G, Nockher WA, et al. Pan-neurotrophin receptor p75 contributes to neuronal hyperreactivity and airway inflammation in a murine model of experimental asthma. Am J Respir Cell Mol Biol, 2003, 28: 170-178.
  5. 5. Ruuskanen O, Ogra PL. Respiratory syncytial virus. Curr Probl Pediatr, 1993, 23: 50-79.
  6. 6. Shen XY, Pan PH, Wu ES, et al. Effects of respiratory syncytial virus infection on the airway neuronal plasticity and its relationship to the bronchial hyperresponsiveness in rats. Chin Med J( Engl) ,2006, 119: 156-159.
  7. 7. Hu CB, Wedde-Beer K, Auais A, et al. Nerve growth factor and nerve growth factor receptors in respiratory syncytial virus-infected lungs. Am J Physiol Lung Cell Mol physiol, 2002, 283: L494-L502.
  8. 8. Hamelmann E, Schwarze J, Takeda K, et al. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med, 1997 ,156: 766-775.
  9. 9. 沈丹華, 廖曉耘, 劉艷麗, 等. 胎盤部位過度反應及胎盤部位結(jié)節(jié)的臨床病理分析, 中華病理學雜志, 2004, 33: 441-444.
  10. 10. Simoes EA. Respiratory syncytial virus infection. Lancet, 1999, 354 :847-852.
  11. 11. Sigurs N, Gustafsson PM, Bjarnason R, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med, 2005, 171: 137-141.
  12. 12. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci, 2001, 24: 677-736.
  13. 13. Delcroix JD, Valletta J, Wu C, et al. Trafficking the NGF signal:implications for normal and degenerating neurons. Prog Brain Res,2004, 146: 3-23.
  14. 14. Huang EJ, Wilkinson GA, Fari　as I, et al. Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo evidence for NT-3 activation of TrkA and TrkB in addition to TrkC.Development, 1999, 126: 2191-2203.
  15. 15. Ringstedt T, Ib　　ez CF, Nosrat CA. Role of brain-derived neurotrophic factor in target invasion in the gustatory system. J Neurosci, 1999, 19: 3507-3518.
  16. 16. Piedimonle G. Contribution of neuroimmune mechanisms to airway inflammation and remodeling during and after respiratory syncytial virus infection. Pediatr Infect Dis J, 2003, 22: S66-S75.
  17. 17. Tortorolo L, Langer A, Polidori G, et al. Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection. Am J Respir Crit Care Med, 2005, 172: 233-237.
  18. 18. Hoffman PN. Distinct Roles of Neurofilament and Tubulin Gene Expression in Axonal Growth. Ciba Found Symp, 1988,138: 192-204.
  19. 19. de Vries A, van Rijnsoever C, Engels F, et al. The role of sensory nerve endings in nerve growth factor-induced airway hyperresponsiveness to histamine in guinea-pigs. Br J Pharmacol, 2001 , 134 :771-776.
  20. 20. de Vries A, Dessing MC, Engels F, et al. Nerve growth factor induces a neurokinin-1 receptor-mediated airway hyperrespon-siveness in guinea pigs. Am J Respir Crit Care Med, 1999, 159: 1541-1544.
  21. 21. Friberg SG, Olgart H　glund C, Gustafsson LE. Nerve growth factor increase airway responssives and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea pig model.Acta Physiol Scand, 2001, 173: 239-245.
  22. 22. Ann NY. Neurotrophins in Allergic Airway Dysfunction What the Mouse Model Is Teching Us. Acad Sci, 2003, 992: 241-249.
  23. 23. 潘頻華, 王慧, 胡成平. 呼吸道合胞病毒感染大鼠脊髓背根節(jié)突觸囊泡素的表達與氣道反應性的關(guān)系. 中國呼吸與危重監(jiān)護雜志, 2007, 6: 294-297.
  24. 24. Randolph CL, Bierl MA, Isaacson LG. Regulation of NGF and NT3 protein expression in peripheral targets by sympathetic input. Brain Res, 2007, 1144: 59-69.

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