脑内注射R-(α)甲基组胺对哮喘大鼠呼吸功能的影响  

Effect of brain injection of R-(α)-methylhistamine on respiratory function in asthmatic rats

作　　者：董榕[1] 胡春梅[2] 王月涵[1] 

机构地区：[1]东南大学基础医学院生理药理学系,南京210009 [2]南京胸科医院,南京210009

出　　处：《中国新药杂志》2008年第22期1919-1923,共5页Chinese Journal of New Drugs

摘　　要：目的:探讨哮喘大鼠孤束核(nucleus tractus solitarius,NTS)内应用组胺H3受体激动剂R-(α)甲基组胺[R-(α)methylhist amine,R-(α)-MeHA]对呼吸运动的影响。方法:根据Elwood的方法,制备哮喘大鼠模型。采用中枢立体定位技术,在NTS脑区微量注射H3受体激动剂R-(α)-MeHA2μg或组胺H3受体拮抗剂thioperamide(Thio)5μg,注射药物体积均为1μL。用电生理方法记录膈肌肌电活动;用胸内压法测定气道阻力和肺顺应性。免疫组织化学方法(SABC法)检测肺内神经源性炎症介质的含量。结果:与正常对照组比较,模型组膈肌放电频率增加,膈肌肌电积分幅值下降,气道阻力增加,肺顺应性降低(均为P<0.01)。与模型组比较,R-(α)-MeHA组膈肌放电频率下降(P<0.01),膈肌肌电积分幅值增加(P<0.05),气道阻力降低(P<0.01),肺顺应性增加(P<0.01),肺内SP样免疫反应阳性物显著减少;Thio组肺功能指标则完全相反,肺内SP样免疫反应阳性物明显增加,差异均有统计学意义。结论:NTS内注射R-(α)甲基组胺能特异性激动脑内组胺H3受体,显著改善哮喘大鼠的肺功能,缓解肺部炎症反应。Objective： To investigate effect of the histamine H3 receptor agonist,R-（α） methylhistamine [R-（α）-MeHA],injected into the nucleus tractus solitarius（NTS） on respiratory function in asthmatic rats.Methods： Rat asthma model was established by Elwood＇s methods.Through a technique of central three-dimensional positioning,a stainless steel jacket was implanted into the NTS,and R-（α）-MeHA 2 μg or thioperamide（Thio,H3 receptor antagonist） 5 μg was injected at a constant speed.The diaphragm EMC activities were recorded by electrophysiological methods.Airway resistance and lung compliance were determined by measuring intrapleural pressures.The levels of neurogenic inflammatory mediators in the lung were detected by immunohistochemistry（SABC）.Results： Compared with the normal control,the diaphragm discharge rate and airway resistance increased;diaphragm EMC amplitude and lung compliance decreased in asthmatic rats（P〈0.01）.R-（α）-MeHA decreased diaphragm discharge rate（P〈0.01）,increased diaphragm EMC amplitude（P〈0.05）,decreased airway resistance（P〈0.01）,improved lung compliance（P〈0.01）,and decreased SP immunoactivities in the lung in asthmatic rats.Thio significantly blocked these effects on lung function,and significantly increased the lung SP immunoactivities.Conclusion： NTS injection of R-（α）-histamine specifically activates histamine H3 receptor in the brain,thereby improves lung function and attenuates lung inflammation in asthmatic rats.

关 键 词：组胺H3受体 R-(α)甲基组胺 孤束核 哮喘 呼吸功能 

分 类 号：R562.25[医药卫生—呼吸系统] R965.1[医药卫生—内科学]