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

中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (2): 128-132.

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

解卫平^1,3, 丁建花¹, 王虹^1,3, 齐栩^1,3, 汪海³, 胡刚¹

¹南京医科大学药理学系, ²第一附属医院呼吸内科, 南京210029, 江苏;
³军事医学科学院药物毒物研究所, 北京100850

收稿日期:2004-12-09 修回日期:2005-01-07 出版日期:2005-02-06 发布日期:2020-11-18
通讯作者: 胡刚, 男, 博士, 教授, 博士生导师, 主要从事分子药理学与临床药理学研究。Tel:025-86663169 E-mail:ghu@njmu.edu.cn
作者简介:解卫平, 女, 博士, 副主任医师, 副教授, 主要从事肺动脉高压的基础与临床研究。
基金资助:
国家创新药物基础研究重大项目基金(No969010101);国家自然科学基金(No39970846);江苏省科委社会发展基金(NoBJ2000051);江苏省教育厅基金(No00KJB320009)

Effects of novel K_ATPCO iptakalim on airway hyperresponsiveness and remodeling in guinea-pigs with asthma

XIE Wei-ping^1,2, DING Jian-hua¹, WANG Hong^1,2, Xu Qi^1,2, WANG Hai³, HU Gang¹

¹Department of Pharmacology & Neurobiology, ²Department of Pulmonology, the First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, Jiangsu, China;
³Beijing Institute of Pharmacology and Toxicology, Molitary Medicine and Science Academic, Beijing 100850, China

Received:2004-12-09 Revised:2005-01-07 Online:2005-02-06 Published:2020-11-18

摘要/Abstract

摘要： 目的:研究新型K_ATP 通道开放剂(K_ATP CO)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Ipt0.75 mg°kg^-1 和1.5 mg°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<0.05);iptakalim(灌服)0.75、1.5 mg°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>0.05)。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(29.8±4.5 μm²°μm^-1)及支气管平滑肌面积(11.7±4.7 μm²°μm^-1)较正常对照组(13.2±5.7,4.4±2.1 μm²°μm^-1)增大(P<0.01), 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>0.05)。结论:口服新型K_ATP 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。

关键词: ATP敏感性钾通道, iptakalim, 哮喘, 气道重构, 气道反应性

Abstract: 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 μm²°μm^-1)was significantly higher than that in the control group (13.2±5.7 μm²°μm^-1, P<0.01).The bronchial smooth muscle thickness in asthmatic group (11.7±4.7 μm²°μm^-1)was significantly higher than that in the control group (4.4±2.1 μm2·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.

Key words: ATP-sensitive potassiumchannel, iptakalim, asthma, airway hyperresponsiveness, airway remodeling

中图分类号:

R966

解卫平, 丁建花, 王虹, 齐栩, 汪海, 胡刚. 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[J]. 中国临床药理学与治疗学, 2005, 10(2): 128-132.

XIE Wei-ping, DING Jian-hua, WANG Hong, Xu Qi, WANG Hai, HU Gang. Effects of novel K_ATPCO iptakalim on airway hyperresponsiveness and remodeling in guinea-pigs with asthma[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(2): 128-132.

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