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中国临床药理学与治疗学 ›› 2002, Vol. 7 ›› Issue (1): 5-8.

• 基础研究 • 上一篇    下一篇

异丙酚、 咪达唑仑抑制交感神经节细胞钠通道电流的联合作用1

郑吉建, 庄心良, 杜冬萍, 茆庆洪, 徐国辉   

  1. 上海市第一人民医院麻醉科, 上海
  • 收稿日期:2001-09-10 修回日期:2001-10-12 出版日期:2002-02-26 发布日期:2020-11-27
  • 通讯作者: 郑吉建,男, 博士, 副教授, 从事麻醉药理学研究。Tel:021-63240090-8101 E-mail:zhengjijian@citiz.net
  • 作者简介:庄心良, 男, 教授, 博士生导师。
  • 基金资助:
    1 上海市医学领先专业重点学科基金资助项目

Combined inhibitory effects of propofol and midazolam on macroscopic sodium currents in rat sympathetic ganglion neurons

ZHENG Ji-Jian, ZHUANG Xin-Liang, DU Dong-Ping, MAO Qing-Hong, XU Guo-Hui   

  1. Department of Anesthesiology, Shanghai First People's Hospital, Shanghai 200080
  • Received:2001-09-10 Revised:2001-10-12 Online:2002-02-26 Published:2020-11-27

摘要: 目的: 研究异丙酚、咪达唑仑对交感神经节细胞钠通道电流的联合作用, 探讨两者复合诱导时循环稳定的可能机制。 方法: 全细胞膜片钳技术记录急性分离 SD 大鼠(7~ 10 d)颈上交感神经节细胞钠通道电流;等辐射线图法分析异丙酚、 咪达唑仑复合对交感神经节细胞钠通道电流的影响。 结果: 在钳制电压(Vh ) 80 mV、 刺激电压(Vt )0 mV条件下, 临床相关浓度的异丙酚、咪达唑仑分别使钠通道电流峰值降低27.66%(P <0.01)和19.98%(P <0.05),随浓度增加,抑制作用逐渐增强,50%的钠通道电流受抑制时的浓度(IC50)分别为 33.12 μmol·L-1 和18.35 μmol·L-1。 1/4、3/4 IC50 的异丙酚与咪达唑仑合用时的 IC50 数值点落在理论上的相加等效线的95%可信区间内; 1/2 IC50 的异丙酚与咪达唑仑合用时的 IC50 数值点落在理论上的相加等效线的 95%可信区间的左下方。结论: 临床相关浓度的异丙酚、 咪达唑仑对交感神经节细胞钠通道电流有明显的抑制作用,且呈浓度依赖性; 除等效剂量合用呈协同抑制作用外, 两者复合主要呈相加抑制交感神经节细胞钠通道流; 复合诱导时循环稳定可能与两者催眠作用明显协同导致诱导剂量的降低, 从而减弱对交感神经的抑制有关。

关键词: 麻醉, 异丙酚, 咪达唑仑, 神经节/交感, 膜片钳, 钠通道, 药物相互作用

Abstract: AIM: To study the interactions of propo-fol and midazolam on the whole-cell sodium channel cur-rents in rat sympathetic ganglion neurons.METHODS: Whole-cell patch-clamp recordings were made from enzy-matically isolated rat (7-10 d)superior cervical sympa-thetic ganglion neurons.Isobolographic analysis was ap-plied to evaluate the potency of combinations of propofol and midazolam on Na+channel currents.RESULTS: Under Vh = 80 mV and Vt =0 mV. Propofol and mida-zolam dose-dependently blocked Na+ currents with a mean drug concentration required to produce 50%current inhibition(IC50 ):33.12 μmol·L-1 and18.35 μmol·L-1; clinically relevant concentrations of propofol and midazo-lam reduced Na+ peak currents by 27.66%(P <0.01) and 19.88%(P <0.05).The IC50 values of midazolam combined with 1/4 and 3/4 IC50 propofol located in the 95% confidence limits of theoretical additive line; the IC50 values of midazolam combined with 1/2 IC50 propofol located under the 95%confidence limitsof theoretical ad-ditive line. CONCLUSION: Clinically relevant concen-trations of propofol and midazolam have direct and dose-dependent inhibition on the Na+ channel currents of rat sympathetic ganglion neurons.The interactions between propofol and midazolam at Na+ channel current are addi-tive, in addition to the synergism which equi-effective doses are used.Reduction of cardiovascular depression during co-inductionof propofol and midazolam may be rel-evant to the reduction of doses.

Key words: anesthesia, propofol, midazolam, sym-pathetic ganglion, patch-clamp/sodium channel, drng in-teraction

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