四种临床常用的钙离子拮抗剂对小鼠抗缺氧能力的影响

Effects of Four Kinds of Familiar Calcium Antagonists on Anti-hypoxia Ability in Mice

目的探讨临床常用于治疗高原反应的4种钙离子拮抗剂———苯磺酸氨氯地平、盐酸地尔硫艹卓、盐酸氟桂利嗪、盐酸维拉帕米对小鼠抗缺氧能力的影响。方法通过建立的常压密闭缺氧小鼠模型和亚硝酸钠血液性缺氧小鼠模型实验、小鼠模拟10 000 m高原急性减压缺氧耐力实验、小鼠密闭缺氧分时段血细胞分析,研究4种典型的钙离子拮抗剂对小鼠抗缺氧能力的影响。结果氨氯地平、氟桂利嗪、维拉帕米的低、高剂量组、地尔硫艹卓各剂量组与对照组相比,能显著延长小鼠在常压密闭缺氧实验中的存活时间(P<0.05,P<0.01)。与对照组比较,氨氯地平低剂量组能延长小鼠在亚硝酸钠血液性缺氧实验及在模拟10 000 m高原急性缺氧耐力实验中的存活时间(P<0.01)。血细胞分析实验中给药组与对照组同时点比较差异无统计学意义(P>0.05)。结论 4种钙离子拮抗剂均有不同程度的提高小鼠抗缺氧能力的作用,而低剂量用药比正常剂量的效果更优,可用于临床指导合理用药。

Objective To explore effects of four kinds of calcium antagonists： Amlodipine Besylate, Diltiazem Hydrochloride, Flunarizine Hydrochloride and Verapamil Hydrochloride in the treatment of altitude sickness on anti-hy- poxia ability in mice, which were widely used in clinic. Methods The anti-hypoxia abilities of mice treated with the four typical kinds of calcium antagonists were studied by establishing normal pressure sealed hypoxic model arid sodium nitrite hemic hypoxia model experiments, testing acute hypoxia endurance to analog 10,000 m altitude, and analyzing time-sharing blood cells of sealed anoxia in mice. Results Survival times of normal pressure sealed hypoxic experiments were significantly prolonged in the low and high dose groups of Amlodipine, Flunarizine and Verapamil, and low, middle and high dose groups of Diltiazem than that in control group（ P 〈 0.05 ,P 〈 0. 01 ）. Survival times of sodium nitrite hemic hypoxia model and acute hypoxia endurance to analog 10,000 m altitude experiments in low dose group of Amlodipine were significantly prolonged than those in control group （P 〈0. 01 ）. The differences showed no statistic significances be- tween medication groups and control group by analysis experiment of blood cells（P 〉 0.05）. Conclusion Four kinds of calcium antagonists may improve anti-hypoxia ability of mice in varying degrees, and the low dose groups may get better effect than the normal dose groups, which can guild rational drug use in clinically.