摘要
目的 比较苦参碱与E 4 0 31,多非利特和RP5 886 6对家兔单个心室肌细胞的内向整流钾电流(Ik1)的效价和效能的不同 ,揭示苦参碱抗心律失常作用弱于西药的原因。方法 应用全细胞膜片钳技术记录苦参碱与E 4 0 31,多非利特和RP5 886 6对家兔Ik1的影响。结果 苦参碱 1和 10 μmol·L- 1对家兔Ik1无明显影响。在实验电压为 - 12 0mV和保持电压为 - 70mV ,苦参碱 5 0和 10 0 μmol·L- 1对Ik1分别抑制达 6 % (n =8,P <0 .0 5 )和 8% (n =8,P <0 .0 5 ) ;在实验电压为 - 5 0mV ,抑制Ik1达 4 % (n =8,P <0 .0 5 )和 8% (n =8,P <0 .0 5 )。在实验电压为 - 12 0mV ,E 4 0 311和 10 μmol·L- 1使Ik1分别降低10 % (n =6 ,P <0 .0 5 )和 4 5 % (n =6 ,P <0 .0 5 )。在 - 5 0mV ,Ik1分别降低 5 % (n =6 ,P <0 .0 5 )和35 % (n =6 ,P <0 .0 5 )。在实验电压为 - 12 0mV ,多非利特 1和 10 μmol·L- 1使Ik1降低 19% (n =8,P <0 .0 5 )及 2 5 % (n =8,P <0 .0 5 )。在 - 5 0mV ,Ik1分别降低 11%和 19% (n =8,P <0 .0 5 )。在实验电压为 - 12 0mV ,RP5 886 6 1和 10 μmol·L- 1使Ik1分别降低 2 1% (n =8,P <0 .0 5 )和 5 0 % (n =8,P <0 .0 5 )。在 - 5 0mV ,Ik1分别降低 6 % (n =8,P <0 .0 5 )和11% (n =8,P <0 .0
AIM To explore the cause of the weaker antiarrhythmic effects o f matrine than that of E-4031, dofetilide and RP58866. METHODS Who le-cell patch-clamp technique was used to record ionic currents in rabbit vent ricular myocytes. RESULTS 1 and 10 μmol·L -1 matrine did not affect the inward rectifier potassium current (I k1). 50 and 1 00 μmol·L -1 matrine reduced I k1 by 6% (n=8, P<0.05) and 8% (n=8, P<0.05), respectively at test potential of - 120 mV from holding potential of -70 mV. At -50 mV, I k1 de creased by 4% (n=8, P<0.05) and 8% (n=8, P<0.05). E-4 031, dofetilide and RP58866 significantly inhibited I k1. At te st potential of -120 mV, 1 and 10 μmol·L -1 E-4031 decreased I k1 by 10% (n=6, P< 0.05) and 45% (n=6, P<0. 05). At -50 mV, I k1 was decreased by 5% (n=8, P< 0.05) and 35% (n=8, P<0.05), respectively. 1 and 10 μmol·L -1 dofetilide decreased I k1 by 19% (n=6, P<0.05) and 25% at -120 mV. At -50 mV, I k1 was decrease d by 11% (n=6, P< 0.05) and 19% (n=6, P<0.05), respec tively. At -120 mV, 1 μmol·L -1 and 10 μmol·L -1 RP58866 decr eased I k1 by 21% (n=8, P<0.05) and 50% (n=8, P<0.05). At -50 mV, I k1 was decreased by 6% ( n=8, P<0.05) and 11% ( n=8, P<0.05), respectivel y. CONCLUSION The lower efficacy and potency of matrine in the in hibitory effects on I k1 than that of E-4031, dofetilide and R P58866 is one of the reasons for weaker antiarrhythmic effects of the Chines e herb than that of pure compounds.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2004年第6期407-414,共8页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金资助项目 (30 2 715 99)~~
