苦参碱对乌头碱诱发的大鼠心室肌细胞电生理改变的作用

苦参碱对乌头碱诱发的大鼠心室肌细胞电生理改变的作用

单宏丽, 杨宝峰^*, 周宇宏, 王赫, 李宝馨

哈尔滨医科大学药理教研室, 黑龙江哈尔滨 150086

收稿日期:2003-09-22 修回日期:2004-08-10 出版日期:2004-09-15 发布日期:2004-09-15
通讯作者: 杨宝峰*

Effects of Matrine on Aconitine-Induced Electrophysiological Changes in Rat Ventricular Myocytes

SHAN Hong-li, YANG Bao-feng^*, ZHOU Yu-hong, WANG He, LI Bao-xin

Department of Pharmacology, Harbin Medical University, Harbin 150086, China

Received:2003-09-22 Revised:2004-08-10 Online:2004-09-15 Published:2004-09-15
Contact: YANG Bao-feng*

摘要/Abstract

摘要： 目的通过比较对不同跨膜离子电流作用的效能、效价, 探讨传统中药苦参碱抗心律失常作用弱于西药奎尼丁、维拉帕米的原因, 确定苦参碱作用的最佳靶点. 方法应用全细胞膜片钳技术记录大鼠单个心室肌细胞动作电位和离子电流. 首先应用乌头碱诱发心肌离子电流改变, 然后观察苦参碱、奎尼丁和维拉帕米对乌头碱诱发离子电流和动作电位改变的作用. 结果乌头碱1μmol·L^-1诱发大鼠单个心室肌细胞动作电位和离子电流显著变化. 乌头碱延长动作电位时程同时增加钠、L-型钙电流和内向整流钾电流. 苦参碱100μmol·L^-1恢复乌头碱诱发的改变, 但作用弱于奎尼丁和维拉帕米. 结论应用乌头碱打破了心室肌细胞离子通道的平衡, 而应用苦参碱明显抑制乌头碱诱发的改变, 但其效能效价低于常用的奎尼丁和维拉帕米.

关键词: 心律失常, 心律失常, 心律失常, 苦参碱, 苦参碱, 苦参碱, 奎尼丁, 奎尼丁, 奎尼丁, 维拉帕米, 维拉帕米, 维拉帕米, 离子通道, 离子通道, 离子通道

Abstract: Aim To explore the reason that the antiarrhythmic effect of the extract of traditional Chinese medicinal herb, matrine, is weaker than quinidine and verapamil by comparision of the effect and efficacy of matrine on various kinds of transmembrane ionic currents with those of quinidine and verapamil; and to demonstrate the best targets for antiarrhythmic drugs. Methods Whole-cell patch-clamp techniques were used to record the action potential and ionic currents in single cells of rat ventricular myocytes. Aconitine was used to induce the changes of ionic currents, then study the effects of matrine and quinidine, verapamil on aconitine-induced imbalanced channel currents and action potential. Results Aconitine 1 μmol·L^-1 induced significant changes in transmembrane currents and action potential in single cells of rat ventricular myocytes. APD was significantly prolonged by aconitine. Simultaneously, aconitine increased sodium, L-type calcium and inward rectifier potassium currents. Matrine 100 μmol·L^-1 reversed the aconitine-induced changes of sodium current (INa) from (-70.2±10.5) pA/pF to (-39.6±4.0) pA/pF (n=5, P<0.05 vs aconitine); L-type calcium current (ICa-L) from (20.4±3.8) pA/pF to (-12.9±2.9) pA/pF (n=6, P<0.01); the inward rectifier potassium current (Ik1) from (-32.2±1.08) pA/pF to (-24.0±3.4) pA/pF (n=6, P<0.01), and action potential duration. The reversal effects of quinidine and verapamil on aconitine-induced changes of APD and ionic currents were more marked than matrine. Conclusion Aco-nitine significantly disturbs the normal equilibrium of ion channels in ventricular myocytes. It induces changes of INa, ICa-L, Ik1 and prolongation of action potential duration. Matrine at concentration 50 or 100 μmol·L-1 statistically significantly suppresses aconitine-induced changes of APD and ionic currents. The potency and efficacy of inhibitory effect of matrine are markedly weaker than those of commonly used verapamil and quinidine.

Key words: arrhythmias, arrhythmias, matrine, matrine, quinidine, quinidine, verapamil, verapamil, ion channel, ion channel

中图分类号:

R965

R972.2

Supporting: Foudation item: National Natural Science Foundation of China (30271599).
^*Corresponding author. Tel.: 86-451-86671354

单宏丽, 杨宝峰^*, 周宇宏, 王赫, 李宝馨. 苦参碱对乌头碱诱发的大鼠心室肌细胞电生理改变的作用[J]. .

SHAN Hong-li, YANG Bao-feng^*, ZHOU Yu-hong, WANG He, LI Bao-xin. Effects of Matrine on Aconitine-Induced Electrophysiological Changes in Rat Ventricular Myocytes[J]. .

参考文献

[1] Atta-Ur-Rahman A, ChoudharyMI, Parvez K, et al. Quinolizidine alkaloids from Sophora alopecuroides [J]. J Nat Prod, 2000, 63 (2): 190-192.
[2] Zhang HM, Li HQ. Anti-arrhythmic effects of sophoridine and oxysophoridine [J]. Acta Pharm Sin, 1999, 20 (6): 517-521.
[3] Li Y, He LR. Studies on effect on cardiovascular system of alkaloid matrine [J]. Chin Tradit Herb Drugs, 2000, 31 (3): 227-229.
[4] Wang XH, Huang SK. Pharmacokinetics and pharmacodynamics of matrine and oxymatrine [J]. Acta Pharm Sin, 1992, 27 (8): 572-576.
[5] Li BX, Yang BF, Zhou J, et al. Inhibitory effects of berberine on Ik1, Ik and HERG channels of cardiac myocytes [J]. Acta Pharm Sin, 2001, 22 (2): 125-131.
[6] Yang BF, Li GR, Nattel S. Effects of RP58866 on transmembrane K⁺ currents in mammalian ventricular myocytes [J]. Acta Pharm Sin, 1999, 20 (11): 961-969.
[7] Yang BF, Luo DL, Bao LH, et al. Artemisinin blocks activating and slowly activating K⁺ current in guinea pig ventricular myocytes [J]. Acta Pharm Sin, 1998, 19 (3): 269-272.
[8] Wang HZ, Yang BF, et al. Direct block of inward rectifier potassium channels by nicotine [J]. Toxicol Appl Pharmacol,2000, 164, 97-101.
[9] Benitah JP, Gomez AM, Fauconnier J, et al. Voltage-gated Ca²⁺ currents in the human pathophysiologic heart: a review [J]. Basic Res Cardiol, 2002, 97 Suppl 1:111-118.
[10] Yang BF, Li GR, Xu CQ et al. Effects of RP58866 on transmembrane K⁺ currents in mammalian ventricular myocytes [J]. Acta Pharm Sin, 1999, 20 (11): 961-969.
[11] Clancy CE, Kass RS. Defective cardiac ion channels: from mutations to clinical syndromes [J]. J Clin Invest, 2002, 110 (8): 1075-1077.
[12] Wright SN. Comparison of aconitine-modified human heart (hH1) and rat skeletal (mu1) muscle Na⁺ channels: an important role for external Na⁺ ions [J]. J Physiol, 2002, 538 (3): 759-771.
[13] Friese J, Gleitz J, Gutser UT et al. Aconitum sp. alkaloids: the modulation of voltage Na⁺ channel, toxicity and antinociceptive properties [J]. Eur J Pharm, 1997, 337 (2-3) 3: 165-174.
[14] Luo M, He P, Wu MC, et al. The preventive effect of matrine on rat hepatoma induced by diethylnitrosamine [J]. Tumor, 2001 ; 21 (4): 239-241.
[15] Li Q, Wang J, Mao XJ, et al. Studies on the cardiotonic activities of oxymatrine [J]. J Shenyang Pharm Univ, 1999, 16 (4): 281-284.
[16] He YJ, Jiang JK, Qu YH, et al. Matrine affects early expression of proto-oncogenes in K562 cells [J]. Cancer, 2002, 21 (4): 369-372.
[17] Ai J, Gao HH, He SZ, et al. Effects of matrine, artemisinin, tetrandrine on cytosolic [Ca²⁺]i in guinea pig ventricular myocytes [J]. Acta Pharma Sin, 2001, 22 (6): 512-515.
[18] Ji Y, Sun LZ, Rao MR, et al. The relationship between the positively inotropic effect of matrine and the cytosolic free calcium concentration [J]. J Nanjing Med Univ, 1998, 18 (4): 265-268.
[19] Zhang BH, Kong XJ, Cai YL. Antiarrhythmic effect of oxymatrine [J]. J Beijing Med Univ, 1988, 20 (6): 530-533.