中枢组胺H_3受体对哮喘豚鼠呼吸运动的影响

THE EFFECT OF CENTRAL HISTAMINE H_3 RECEPTOR ON BREATHING ACTIVITY OF ASTHMATIC GUINEA PIGS

目的:探讨中枢组胺H3受体与哮喘发病的关系。方法:动物经侧脑室插管给药后,记录膈肌放电活动(DA)和呼吸频率(RR)。免疫组织化学方法检测下呼吸道内SP样免疫反应物的含量。荧光分光光度法测定脑内组胺含量。结果:①静脉注射卵蛋白(0.1mg/kg)诱发哮喘急性发作后,动物RR加快,DA幅度减小,同时下呼吸道内SP样免疫反应物的数量明显增加(P<0.01),下丘脑和皮质内组胺含量增多(P<0.01)。②哮喘急性发作后,侧脑室注射H3受体激动剂RAMH(5μg)后,与哮喘组相比,RR明显降低,DA幅度明显增加(P<0.01)。下呼吸道内SP样免疫反应物的数量明显减少(P<0.01)。③哮喘缓解期,侧脑室注射组胺H3受体拮抗剂THIO(20μg)后,RR明显加快,DA幅度减小。下丘脑和皮质内组胺含量均高于对照组(P<0.05)。结论:脑内组胺H3受体参与了对哮喘发作的神经性调控过程。

Aim： To investigate the effect of selective H3 receptor agonist （R）-α-methylhistamine and antagonist thioperamide on the respira- tory response in asthmatic guinea pigs respectively. Methods： Anesthesized guinea pigs were prepared with a implanted intraeere- broventricular（icv） cannula and instrumented for the measurement of respiratory rate（RR） and diaphragmatic electric activity（DA）. Substance P-like immunoreactive（SP-LI） substances in lower respiratory tract were detected by immunohistochemical method. Brain histamine contents were measrued by fluorometric determination. Results： ① Intravenous injection of ovalbumin caused tachypnea and significant decrease in DA magnitude. At the same time, SP-LI substances increased in trachea , bronchus and lung. ②Administration of selective H3 receptor agonist（R）-α-methylhistamine（5μg） icv immediately after iv ovalbumin could significantly ameliorate the changes in RR and DA induced by ovalbumin. In accordance, SP-LI substances in lower respiratory tract markedly decreased at 5 min and 10 min after（R）-α-methylhistamine microinjection. ③Icv thioperamide（20μg） caused a significant increase in RR and a decrease in DA. ④ Brain histamine contents increased in hypothalamus and cortex during asthma. After mieroinjection of thioperamide（20 μg） iev significant increase of histamine contents in hypothalamus and cortex was observed. Conclusion： Brain histamine H3 receptors may be related to asthmatic respiratory responses.