下丘脑乳头体核对哮喘大鼠呼吸运动的调控作用研究
|
摘要
目的研究下丘脑后区结节乳头体核(TMN)组胺能神经元在哮喘发作中的作用。方法取72只健康雄性SD大鼠作为研究对象,其中64只通过腹腔注射卵蛋白(OA)致敏,雾化吸入OA溶液诱发哮喘发作,制作大鼠哮喘模型,余8只作为对照。在麻醉状态下通过静脉注射OA溶液诱发大鼠哮喘发作,用生物信号采集系统记录下丘脑后区结节乳头体核(TMN)电活动,并进行功能谱分析。利用中枢立体定位技术,分别对TMN进行电刺激与电损毁;通过中枢核团微量注射技术,在TMN内分别微量注射组胺H3受体激动剂R-α-Me-HA与拮抗剂THIO,检测膈肌放电频率及积分、每分通气量、呼气与吸气时程比、气道阻力和肺顺应性等肺功能指标。结果与正常对照大鼠比较,哮喘大鼠TMN放电组的α波,β1与β2波所占比例升高,δ波和θ波的比例降低,放电总功率升高。与对照大鼠比较,采用电刺激哮喘大鼠TMN以及在TMN内微量注射组胺H3受体拮抗剂时,大鼠膈肌肌电频率、呼气/吸气比和气道阻力均增加,膈肌肌电积分、每分通气量和肺顺应性减小。而采用电损毁哮喘大鼠TMN以及在TMN内微量注射组胺H3受体激动剂后,膈肌肌电频率、呼气/吸气比和气道阻力均减小,膈肌肌电积分、每分通气量和肺顺应性增加。结论下丘脑后区TMN核团活动可影响哮喘大鼠的呼吸活动。
Objective To explore the role of central histaminergic neurons in the tuberomammillar y nucleus(TMN) of posterior hypothalamus on asthma. Methods Seventy-two healthy male SD rats were served as study objects. Sixty-four rats were sensitized with ovalbumin(OA) solution intraperitoneally and challenged with OA aerosol inhalation to prepare asthma model. Asthma attack was evoked in asthmatic rats by OA solution injected intravenously, the electrical activities of TMN in posterior hypothalamus were recorded with biological signal collecting system and the power spectra were analyzed. TMN was lesioned or stimulated electrically by central stereo positioning technology. Histamine H3 receptor agonist R-(α)-methylhistamine(RMHA) or antagonist thioperamide(THIO) was microinjected into TMN by central nuclear group microinjection technology, and the pulmonary function indexes were detected incl uding diaphragm electromyography(EMGdi) frequency, EMGdi integral, minute ventilation volume(MVV), expiratory time/inspiratory time(TE/TI), airway resistance(Raw) and dynamic pulmonary compliance(Cdyn). Results Compared with control group, the percentage of α, β1 and β2 wave in the electrical activities of TMN of asthmatic rats increased significantly, while the percentage of δ and θ wave decreased and the total discharge power increased. Compared with the corresponding control group, electric lesion of TMN or TMN microinjected with histamine H3 receptor antagonist increased EMGdi frequency, TE/TI, Raw, and decreased EMGdi integral, MVV and Cdyn. Compared with the corresponding control group, electric stimulation of TMN or TMN microinjected with histamine H3 receptor agonist decreased EMGdi frequency, TE/TI, Raw, and increased EMGdi integral, MVV and Cdyn. Conclusion Central histaminergic neurons in tuberomammillary nucleus of posterior hypothalamus are activated in asthmatic rats.
Objective To explore the role of central histaminergic neurons in the tuberomammillar y nucleus(TMN) of posterior hypothalamus on asthma. Methods Seventy-two healthy male SD rats were served as study objects. Sixty-four rats were sensitized with ovalbumin(OA) solution intraperitoneally and challenged with OA aerosol inhalation to prepare asthma model. Asthma attack was evoked in asthmatic rats by OA solution injected intravenously, the electrical activities of TMN in posterior hypothalamus were recorded with biological signal collecting system and the power spectra were analyzed. TMN was lesioned or stimulated electrically by central stereo positioning technology. Histamine H3 receptor agonist R-(α)-methylhistamine(RMHA) or antagonist thioperamide(THIO) was microinjected into TMN by central nuclear group microinjection technology, and the pulmonary function indexes were detected incl uding diaphragm electromyography(EMGdi) frequency, EMGdi integral, minute ventilation volume(MVV), expiratory time/inspiratory time(TE/TI), airway resistance(Raw) and dynamic pulmonary compliance(Cdyn). Results Compared with control group, the percentage of α, β1 and β2 wave in the electrical activities of TMN of asthmatic rats increased significantly, while the percentage of δ and θ wave decreased and the total discharge power increased. Compared with the corresponding control group, electric lesion of TMN or TMN microinjected with histamine H3 receptor antagonist increased EMGdi frequency, TE/TI, Raw, and decreased EMGdi integral, MVV and Cdyn. Compared with the corresponding control group, electric stimulation of TMN or TMN microinjected with histamine H3 receptor agonist decreased EMGdi frequency, TE/TI, Raw, and increased EMGdi integral, MVV and Cdyn. Conclusion Central histaminergic neurons in tuberomammillary nucleus of posterior hypothalamus are activated in asthmatic rats.
引文
[1]Seil S,Hamid A,Lena U.Translational value of animal models of asthma:Challenges and promises[J].Eur J Pharmacol,2015,759:272-277.
[2]Yan ZQ,Hong JK,Li DB,et al.Ex pression of histamine H4receptor in nasal mucosa of rats with allergic rhinitis[J].Med J Chin PL A,2010,35(7):857-859.[燕志强,洪锦科,李得本,等.组胺H4受体在变应性鼻炎大鼠鼻黏膜中的表达[J].解放军医学杂志,2010,35(7):857-859.]
[3]Martin M,Kazutaka M.The metabolism of histamine in rat hypothalamus and cor tex af ter reser pine treatment[J].Neurochem Int,2015,85-86:31-39.
[4]Blindow S,Preisser A M,Baur X,et al.Is the analysis of histamine and/or interleuk in-4 release af ter i soc yanate chal lenge usef ul in the identif ication of patients w ith Ig Emediated isocyanate asthma[J]?J Immunol Methods,2015,422:35-50.
[5]Ji J,Dong R.Effect of histamine H3 receptor in the hypothalamic paraventricular nucleion hypoth-alamic-pituitary-adrenal axis in rats with asthma[J].Acta Univ Med Nanjing,2011,31(1):40-43.[季吉,董榕.下丘脑室旁核组胺H3受体对哮喘大鼠下丘脑垂体肾上腺轴功能的调控[J].南京医科大学学报(自然科学版),2011,31(1):40-43.]
[6]Brown RE,Stevens DR,Haas HL.The physiolog y of brain histamine[J].Prog Neurobiol,2001,63(6):637-672.
[7]Jarskog LF,Lowy MT,Grove R A,et al.A Phase II study of a histamine H receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy[J].Schizophr Res,2015,164(1-3):136-142.
[8]Passani MB,Blandina P.Histamine receptors in the CNS as targets for therapeutic inter vention[J].Trends Pharmacol Sci,2011,32(4):242-249.
[9]Matsumoto K,Aizawa H,Fukuyama S,et al.Low-dose salbutamol suppresses air way responsiveness to histamine but not methacholine in subjects with asthma[J].Respir Investig,2013,51(3):158-165.
[10]Dong Rong,Zhang Min,Liu BS.The effect of central histamine H3 rececptor on breathing activity of asthmatic guinea pigs[J].Chin J Appl physiol,2006,22(1):117-121.[董榕,张敏,刘保森.中枢组胺H3受体对哮喘豚鼠呼吸运动的影响[J].中国应用生理学杂志,2006,22(1):117-121.]
[11]Hu CM,Dong R,Liu BS,et al.Effect of histamine H3 receptors in nucleus tractus solitaries on c-Fos expression in the brain of rats with asthma onset[J].J Southest Univ(Med Sci Edi),2005,24(6):371-374.[胡春梅,董榕,刘保森,等.大鼠孤束核H3受体对哮喘发作时脑组织中Fos蛋白表达的影响[J].东南大学学报,2005,24(6):371-374.]
[12]Shen HF,Zhang XH,Zhu XJ,et al.Effects of chronic ethanol exposure on the EEG and power spectra in rat nucleus accumben[J].Chin J Neurosci,2002,18(1):446-450.[沈红芬,张晓虎,朱学江,等.慢性酒精刺激对大鼠伏核EEG及脑电功率谱的影响[J].中国神经科学杂志,2002,18(1):446-450.]
[13]Din h-Xuan A T,Annesi-Maesano I,Berger P,et al.Contribution of exhaled nitric oxide measurement in air way i nflammation ass essment in asthma[J].Rev Mal Respir,2015,32(2):193-215.
[14]Hu H.Cough variant asthma:progress in diagnosis and treatment[J].Med J Chin PL A,2014,39(5):361-364.[胡红.咳嗽变异性哮喘的诊断及治疗进展[J].解放军医学杂志,2014,39(5):361-364.]
[15]Liu NN,Dong R,L iang Y,et al.Study on the act iv it ies of amy gda la in the models of asthma and its mechanisms[J].Chinese Journal of Neuroanatomy,2008,24(3):292-296.[刘伲娜,董榕,梁韵,等.杏仁核参与大鼠哮喘发作及其机制探讨[J].神经解剖学杂志,2008,24(3):292-296.]
[16]Ellenbroek BA,Ghiabi B.The other side of the histamine H3receptor[J].Trends Neurosci,2014,37(4):191-199.
[17]Ha xhiu MA,Rust CF,Brooks C,et al.CNS determinants of sleep-related worsening of air way functions:Implications for nocturnal asthma[J].Respir Physiol Neurobiol,2006,151(1):1-30.
[18]Harkness LM Ashton AW,Burgess JK.Asthma is not only an airway disease,but also a vascular disease[J].Pharmacol Ther,2015,148:17-33.
[2]Yan ZQ,Hong JK,Li DB,et al.Ex pression of histamine H4receptor in nasal mucosa of rats with allergic rhinitis[J].Med J Chin PL A,2010,35(7):857-859.[燕志强,洪锦科,李得本,等.组胺H4受体在变应性鼻炎大鼠鼻黏膜中的表达[J].解放军医学杂志,2010,35(7):857-859.]
[3]Martin M,Kazutaka M.The metabolism of histamine in rat hypothalamus and cor tex af ter reser pine treatment[J].Neurochem Int,2015,85-86:31-39.
[4]Blindow S,Preisser A M,Baur X,et al.Is the analysis of histamine and/or interleuk in-4 release af ter i soc yanate chal lenge usef ul in the identif ication of patients w ith Ig Emediated isocyanate asthma[J]?J Immunol Methods,2015,422:35-50.
[5]Ji J,Dong R.Effect of histamine H3 receptor in the hypothalamic paraventricular nucleion hypoth-alamic-pituitary-adrenal axis in rats with asthma[J].Acta Univ Med Nanjing,2011,31(1):40-43.[季吉,董榕.下丘脑室旁核组胺H3受体对哮喘大鼠下丘脑垂体肾上腺轴功能的调控[J].南京医科大学学报(自然科学版),2011,31(1):40-43.]
[6]Brown RE,Stevens DR,Haas HL.The physiolog y of brain histamine[J].Prog Neurobiol,2001,63(6):637-672.
[7]Jarskog LF,Lowy MT,Grove R A,et al.A Phase II study of a histamine H receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy[J].Schizophr Res,2015,164(1-3):136-142.
[8]Passani MB,Blandina P.Histamine receptors in the CNS as targets for therapeutic inter vention[J].Trends Pharmacol Sci,2011,32(4):242-249.
[9]Matsumoto K,Aizawa H,Fukuyama S,et al.Low-dose salbutamol suppresses air way responsiveness to histamine but not methacholine in subjects with asthma[J].Respir Investig,2013,51(3):158-165.
[10]Dong Rong,Zhang Min,Liu BS.The effect of central histamine H3 rececptor on breathing activity of asthmatic guinea pigs[J].Chin J Appl physiol,2006,22(1):117-121.[董榕,张敏,刘保森.中枢组胺H3受体对哮喘豚鼠呼吸运动的影响[J].中国应用生理学杂志,2006,22(1):117-121.]
[11]Hu CM,Dong R,Liu BS,et al.Effect of histamine H3 receptors in nucleus tractus solitaries on c-Fos expression in the brain of rats with asthma onset[J].J Southest Univ(Med Sci Edi),2005,24(6):371-374.[胡春梅,董榕,刘保森,等.大鼠孤束核H3受体对哮喘发作时脑组织中Fos蛋白表达的影响[J].东南大学学报,2005,24(6):371-374.]
[12]Shen HF,Zhang XH,Zhu XJ,et al.Effects of chronic ethanol exposure on the EEG and power spectra in rat nucleus accumben[J].Chin J Neurosci,2002,18(1):446-450.[沈红芬,张晓虎,朱学江,等.慢性酒精刺激对大鼠伏核EEG及脑电功率谱的影响[J].中国神经科学杂志,2002,18(1):446-450.]
[13]Din h-Xuan A T,Annesi-Maesano I,Berger P,et al.Contribution of exhaled nitric oxide measurement in air way i nflammation ass essment in asthma[J].Rev Mal Respir,2015,32(2):193-215.
[14]Hu H.Cough variant asthma:progress in diagnosis and treatment[J].Med J Chin PL A,2014,39(5):361-364.[胡红.咳嗽变异性哮喘的诊断及治疗进展[J].解放军医学杂志,2014,39(5):361-364.]
[15]Liu NN,Dong R,L iang Y,et al.Study on the act iv it ies of amy gda la in the models of asthma and its mechanisms[J].Chinese Journal of Neuroanatomy,2008,24(3):292-296.[刘伲娜,董榕,梁韵,等.杏仁核参与大鼠哮喘发作及其机制探讨[J].神经解剖学杂志,2008,24(3):292-296.]
[16]Ellenbroek BA,Ghiabi B.The other side of the histamine H3receptor[J].Trends Neurosci,2014,37(4):191-199.
[17]Ha xhiu MA,Rust CF,Brooks C,et al.CNS determinants of sleep-related worsening of air way functions:Implications for nocturnal asthma[J].Respir Physiol Neurobiol,2006,151(1):1-30.
[18]Harkness LM Ashton AW,Burgess JK.Asthma is not only an airway disease,but also a vascular disease[J].Pharmacol Ther,2015,148:17-33.