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作 者:宋奇颖 郭鹏美 董丽娜[1] 董苗苗 刘宇[1] SONG Qiying;GUO Pengmei;DONG Lina;DONG Miaomiao;LIU Yu(Department of Pharmacology,Shanxi Medical University,Taiyuan 030001,China)
出 处:《中国比较医学杂志》2018年第5期65-69,共5页Chinese Journal of Comparative Medicine
基 金:国家自然科学基金资助项目(编号:81603111);山西省"1331工程"重点学科建设计划支持学科
摘 要:目的探讨氯硝柳胺乙醇胺盐(niclosamide ethanolamine,NEN)对离体大鼠冠状动脉(rat coronary artery,RCA)的舒张作用及其机制。方法采用微血管张力法测定RCA血管张力,观察NEN对预收缩血管的舒张作用;通过抑制剂实验探讨NEN舒张RCA与钾通道和MAPK信号通路的关系;通过观察NEN对血管收缩剂所致的在去钙和复钙液中收缩的影响,探讨NEN的作用与细胞内外钙的关系。结果 NEN(0.5~3.0μmol/L)对KCl或U46619所致的RCA收缩均具有浓度依赖性的舒张作用。MAPK抑制剂PD98059和SB239063减弱NEN的舒张作用,而钾通道阻断剂四乙胺、4-氨基吡啶、氯化钡和格列本脲对NEN的舒张作用无显著影响。NEN减弱KCl或U46619所致的细胞外钙内流依赖性RCA收缩,而对细胞内钙释放依赖性RCA收缩无显著影响。结论 NEN对离体RCA有显著的舒张作用,其机制可能与其激活MAPK信号通路、抑制细胞外钙内流有关。Objective To investigate the vasorelaxant effect and possible mechanism of niclosamide ethanolamine(NEN) on isolated rat coronary artery(RCA). Methods Wire myograph was used to record myogenic tone of vessels.The vasorelaxant effect of NEN was studied in RCA precontracted with either KCl or U46619. Study of related inhibitors was performed to investigate possible involvement of potassium channels and the mitogen-activated protein kinase(MAPK)signaling pathway in vasorelaxation. The effect of NEN on Ca^2+mobilization was determined by observing vasoconstrictorinduced contractions in tissue solution deprived of Ca^2+followed by Ca^2+restoration. Results NEN(0. 5-3. 0 μmol/L)relaxed RCA precontracted with KCl or U46619 in a concentration-dependent manner. MAPK inhibitors(PD98059 and SB239063) reduced the relaxant effect of NEN,while the potassium-channel blockers(tetraethylamine,4-aminopyridine,BaCl2,and glibenclamide) did not significantly affect relaxation. NEN specifically inhibited the contraction component dependent on extracellular Ca^2+influx in vessels stimulated with KCl and U46619,with a negligible effect on the component dependent on intracellular Ca^2+release. Conclusions NEN exhibits vasodilator properties in RCA. Inhibitionof extracellular Ca^2+influx and activation of the MAPK signaling pathway may be involved in NEN-induced RCA vasorelaxation.
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