埃他卡林对间歇性低氧暴露肺微动脉的选择性扩张作用  

The selective dilatation effects of iptakalim on pulmonary arterioles in hypoxic pulmonary hypertensive rat

作　　者：黄景慧[1] 韩文志[1] 张雁芳[1] 段瑞峰[1] 邓浩浩[1] 郭玉红[1] 刘卫[1] 汪海[1,2] 

机构地区：[1]军事医学科学院卫生学环境医学研究所心血管药物研究中心,北京100850 [2]北京赛德维康医药研究院,北京100039

出　　处：《中国应用生理学杂志》2013年第4期333-336,共4页Chinese Journal of Applied Physiology

基　　金：国家新药创制科技重大专项(2010 ZX 09401-307-1-9);军队"十二五"重大专项(AWS11J003);国家973计划(2009CB521804);国家自然科学基金(81171870)

摘　　要：目的：研究新型ATP敏感性钾通道开放剂埃他卡林（Ipt）对间歇性低氧暴露肺微动脉扩张作用特征。方法：将雄性SD大鼠随机分为3组,对照组（Control）,低氧暴露组,置于常压低氧舱内（O210%±0.5%）8 h/d,每周6d,和低氧暴露＋醋氮酰胺（Acz）干预组（灌胃给予Acz 80 mg/（kg.d））。12周后分离大鼠管径为（197±4）μm的肺微动脉组织,利用DMT微血管张力测定仪在6 nmol/L内皮素-1（ET-1）致血管预收缩条件下,考察不同浓度Ipt对间歇性低氧暴露肺微动脉张力变化并利用ACh考察肺微动脉内皮活性。结果：与常压常氧组对比,10-5mol/LACh对间歇性低氧暴露肺微动脉舒张率显著降低（P〈0.01）,而与80 mg/kg Acz干预组肺微动脉舒张率无显著性差异（P〉0.05）;Ipt在（10-11~10-4）mol/L对间歇性低氧暴露肺微动脉呈剂量依赖性舒张作用,与80 mg/kg Acz干预组间无显著性差异（P〉0.05）,而对常压常氧组肺微动脉无明显的舒张作用。结论：间歇性低氧暴露肺微动脉内皮细胞功能受损,Ipt可选择性扩张低氧暴露肺微动脉;Acz可改善低氧所致内皮细胞功能异常,但并不影响Ipt对低氧暴露肺微动脉的选择性扩张作用。Objective： To study the selective dilatation effects of iptakalim（Ipt）,a novel ATP-sensitive potassium channel opener,on pulmonary arterioles in hypoxic pulmonary hypertensive rat.Methods： SD male rats were divided into 3 groups,control group,the rest were fed in hypoxic and normobaric environment（O2 10%±0.5%,8 h/d and 6 d/week） and divided into hypoxia group and hypoxia plus acetazolamide（Acz） group（hypoxic rats were treated with ig acetazolamide（Acz） 80 mg·kg-1·d-1）.After 12 weeks,pulmonary arteriole rings about（197±4）μm were isolated and the tension of hypoxic pulmonary arterioles pre-contracted by 6 nmol/L endothelin-1（ET-1） was observed with wire myograph system model（DMT 610 m）.The relaxing response of hypoxic pulmonary arterioles induced by different concentration of Ipt were detected and endothelial activity was also tested by acetylcholine.Results： 10-5 mol/L acetylcholine（ACh）-mediated vasodilatation was greatly reduced in the hypoxic group than those in control group（P＆lt;0.01） and there was no significant difference between Acz treatment group and control group（P＆gt;0.05）.Ipt at the concentration ranging from 10-11 mol/L to 10-4 mol/L,caused dose dependent vasodilation on both hypoxic pulmonary arterioles and Acz treatment group（P＆gt;0.05）,but not on normal group.Conclusion： The endothelial function of pulmonary arterioles was damaged under hypoxic pulmonary hypertensive state,and Ipt showed selective dilatation effects on hypoxic pulmonary arterioles.Acz could improve the dysfunction of endothelial cells induced by hypoxic pulmonary hypertensive state,which didn’t affect the selective dilatation effects of Ipt on hypoxic pulmonary arterioles.

关 键 词：埃他卡林 低氧 肺动脉高压 肺微动脉 微血管内皮 

分 类 号：R332[医药卫生—人体生理学] R972.4[医药卫生—基础医学]