新型K_(ATP)开放剂iptakalim对豚鼠哮喘模型气道反应性及其结构的影响  

Effects of novel K_(ATP) CO iptakalim on airway hyperresponsiveness and remodeling in guinea pigs with asthma

作　　者：解卫平[1] 丁建花[1] 王虹[1] 齐栩[1] 汪海[2] 胡刚[1] 

机构地区：[1]南京医科大学药理学系 [2]军事医学科学院药物毒物研究所,北京100850

出　　处：《中国临床药理学与治疗学》2005年第2期128-132,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家创新药物基础研究重大项目基金 (№ 9690 10 10 1) ;国家自然科学基金 (No3 9970 846) ;江苏省科委社会发展基金 (№BJ2 0 0 0 0 5 1) ;江苏省教育厅基金 (№ 0 0KJB3 2 0 0 0 9)

摘　　要：目的 :研究新型KATP 通道开放剂 (KATPCO )iptakalim对哮喘豚鼠气道重塑、气道高反应性的作用。方法 :卵蛋白 (OA)制作哮喘模型 ,地塞米松组在吸入OA前先给予地塞米松 ;iptakalim高剂量治疗组和低剂量治疗组每天吸入OA前分别灌胃给Ipt0 .75mg·kg-1和 1.5mg·kg-1。用多道生理记录仪记录豚鼠气管螺旋条对不同浓度组织胺的收缩反应性 ;用图像分析仪测定细支气管内周长 (PI)、管壁面积 (WA)、管壁平滑肌面积 (SA) ,PI对WA、SA进行标准化 ,分别以WA PI、SA PI表示。结果 :组织胺可使各组豚鼠气管螺旋条产生剂量依赖性收缩。哮喘组豚鼠气管螺旋条对组织胺的收缩反应明显高于正常组 (P <0 .0 5 ) ;iptakalim(灌服 ) 0 .75、1.5mg·kg-1均具有同雾化吸入地塞米松相似的降低气管螺旋条收缩反应效果 (P >0 .0 5 )。对无软骨且平滑肌成环的细支气管图像分析显示 ,哮喘组豚鼠支气管壁面积 (2 9.8± 4 .5 μm2 ·μm-1)及支气管平滑肌面积(11.7± 4 .7μm2 ·μm-1)较正常对照组 (13.2± 5 .7,4 .4± 2 .1μm2 ·μm-1)增大 (P <0 .0 1) ,iptakalim使豚鼠管壁厚度和平滑肌厚度明显下降 ,与正常组比较差异不显著 (P >0 .0 5 )。结论 :口服新型KATP 通道开放剂iptakalim可抑制哮喘豚鼠气道高反应性和气道壁的重构。AIM: To investigate the antiasthmatic effects of novel K ATP CO iptakalim on airway hyperresponsiveness and remodeling in guinea pigs with asthma. METHODS: Thirty guinea pigs were randomly assigned to five groups:control group, asthma group, iptakalim 0.75 group (asthmatic guinea pigs treated with iptakalim 0.75 mg·kg -1 ·d -1 , ig), iptakalim 1.5 group (asthmatic guinea pigs treated with iptakalim 1.5 mg·kg -1 ·d -1 , ig), and dexamethasone (Dex) group . The reactivity of tracheal stripe in various concentrations of histamine was measured. The airway internal perimeter, wall area and bronchial smooth muscle thickness were measured by image analysis system in all groups. RESULTS: The sensitivity of tracheal stripe to histamine was significantly higher in asthma group than that in the control group. Both doses of iptakalim could markedly reduce responsiveness of tracheal stripe to the histamine. The airway wall thickness(WA/PI) in asthmatic group ( 29.8 ± 4.5 μm 2·μm -1 ) was significantly higher than that in the control group ( 13.2 ± 5.7 μm 2·μm -1 , P< 0.01 ). The bronchial smooth muscle thickness in asthmatic group ( 11.7 ± 4.7 μm 2·μm -1 ) was significantly higher than that in the control group ( 4.4 ± 2.1 μm 2·μm -1 ,P< 0.05 ). The airway wall thickness (WA/PI) and bronchial smooth muscle thickness in the two iptakalim groups were increased slightly compared with these in the control group, but there were no significantly differences between them in statistic (P> 0.05 ). CONCLUSION: iptakalim can reduce the airway hyperresponsiveness and remodeling in guinea pigs with asthma.

关 键 词：ATP敏感性钾通道 IPTAKALIM 哮喘 气道重构 气道反应性 

分 类 号：R966[医药卫生—药理学]