摘要
目的 研究第3代二氢吡啶类钙通道拮抗剂贝尼地平对氯化钾(KCl)引起的人乳内动脉收缩的拮抗作用,探讨冠状动脉旁路移植术中使用贝尼地平作移植血管解痉剂的可能性.方法 收集19例冠心病患者移植术中废弃的乳内动脉,每例裁剪为3 mm长,置于微血管张力测定仪中.两种方法研究贝尼地平对离体乳内动脉的药理反应:(1)贝尼地平对KCl预收缩血管的舒张效应(7例).用K+(KCl 40 mmol/L)预收缩乳内动脉后,加入累计终浓度为 10-11~ 10-4.5 mol/L的贝尼地平溶液.(2)贝尼地平预孵育后,对KCl收缩血管的抑制作用(6例).将同一根乳内动脉切成2段,分为实验组和对照组.实验组加入浓度10-8 mol/L贝尼地平(相当于人体内平均稳态血药浓度),对照组加入相应体积的水(对照溶剂),分别孵育 1 h,加入累计浓度的血管收缩剂KCl(5~ 120 mmol/L).贝尼地平孵育24 h后,采用酶联免疫吸附法检测caveolin 1.2蛋白的含量(3份,每份2例).结果 舒张效应实验中,贝尼地平引起KCl预收缩血管的最大舒张百分比为(87.7±4.9)%.拮抗效应实验中,经贝尼地平孵育后,血管最大收缩值为(9.1±3.4)mN,与加入相同体积水的对照组相比有统计学差异[(16.9±4.4)mN,P<0.01].贝尼地平孵育后,对KCl有很好的拮抗效应(P<0.05),caveolin 1.2含量明显降低(P<0.05).结论 贝尼地平对KCl引起的血管收缩作用有很好的拮抗作用,其对血管的舒张作用可能与caveolin 1.2的表达相关.冠状动脉旁路移植术中使用贝尼地平能有效预防和治疗血管痉挛.
Objective To investigate the antagonism of third generation dihydropyridine calcium channel antagonist beni-dipine in contraction induced by potassium chloride(KCl)in human internal mammary artery(IMA),and in order to explore the possibility of using benidipine as an antispastic agent during coronary artery bypass grafting(CABG). Methods The IMAs were taken from 19 patients undergoing CABG. The vasodilator effect(n = 7)on KCl-induced contraction and the inhibition effect(n = 6)after incubation with benidipine were studied in a myograph. The caveolin 1. 2 was detected(n = 3,2 cases re-spectively)by enzyme-linked immunosorbent assay (ELISA). Results The maximum relaxation caused benidipine was (87. 7 ± 4. 9)% . Incubation with benidipine significantly depressed the contraction by KCl[from( 16. 9 ± 4. 4)mN to (9. 1 ± 3. 4 )mN,P < 0. 01]. The concentration of caveolin 1. 2 was down-regulated after incubation with benidipine(P < 0. 05). Conclusion Benidipine has a potent inhibitory effect on KCl-induced vasoconstriction. The relaxation may be related with the expression of caveolin 1. 2. Using benidipine in patients undergoing CABG may provide antispastic effects in grafts.
作者
侯海涛
王君
王正清
高卫真
何国伟
Hou Haitao;Wang Jun;Wang Zhengqing;Gao Weizhen;He Guowei(Clinic for Cardiovascular Diseases,Tianjin Medical University,Basic Medical Research Center of TEDA International Cardiovas-cular Hospital,Tianjin 300457,China;Department of Pharmacology,Tianjin Medical University,Tianjin 300070,China)
出处
《中华胸心血管外科杂志》
CSCD
北大核心
2018年第11期694-696,共3页
Chinese Journal of Thoracic and Cardiovascular Surgery
基金
天津市滨海新区卫生计生委科技项目(2016BWKY007).
关键词
贝尼地平
冠状动脉旁路移植
钙通道拮抗剂
血管痉挛
Benidipine
Coronary artery bypass grafting
Calcium channel blockers
Grafts spasm