Antiarrhythmic Properties of Long-Term Treatment with Matrine in Arrhythmic Rat Induced by Coronary Ligation

被引:60
作者
Li, Xuelian [1 ]
Chu, Weiming [1 ]
Liu, Jinling [1 ]
Xue, Xiaorong [1 ]
Lu, Yanjie [1 ,2 ]
Shan, Hongli [1 ]
Yang, Baofeng [1 ,2 ]
机构
[1] Harbin Med Univ, Dept Pharmacol, State Prov Key Labs Biomed Pharmaceut China, Harbin 150081, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Cardiovasc Res Inst, Harbin 150081, Heilongjiang, Peoples R China
关键词
matrine; arrhythmia; potassium current; myocardial infarction; intracellular calcium; PIG VENTRICULAR MYOCYTES; POSTMYOCARDIAL INFARCTION TREATMENT; MYOCARDIAL-INFARCTION; GUINEA-PIG; HEART-FAILURE; K+ CURRENTS; INTRACELLULAR CALCIUM; EXPRESSION; TRANSIENTS; CHANNELS;
D O I
10.1248/bpb.32.1521
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Matrine, a monomer of traditional Chinese medicine Sophora flavescens, is a potential drug for treatment of arrhythmia. The aim of the study is to elucidate the protective effects of matrine on arrhythmic rat induced by myocardial infarction (MI) and further explore underlying targets. Experiments were performed to investigate the effects of long-term oral administration of matrine on coronary ligation induced arrhythmia, measured in whole animals, via surface electrocardiogram (ECG). Whole-cell patch-clamp technique was used to record the action potential and potassium ionic currents in myocytes isolated from rat hearts. The cytoplasmic free Ca2+ concentration ([Ca2+](i)) was measured using the scanning confocal microscopy. Mortality rate was 19/30 (63%) in MI group and 10130 (33%) in matrine group (p<0.05). This represented a 1.9-fold reduction in long-term mortality rate. The prolonged action potential duration (APD) induced by MI were significantly shortened by long-term treatment of matrine. Matrine restored Kv4.2/I-to, Kir2.1/I-K1 in rat ventricular myocytes after MI. Abnormaly decreased [Ca2+](i) mediated by ischemia can be recovered by matrine. Our results suggested that long-term oral administration of matrine reduced arrhythmia and mortality. Electrophysiological experiment revealed that long-term matrine treatment played an important role in anti-arrhythmia through ionic mechanism. Knowledge of matrine from this work may provide insight into the development of new drugs for long-term myocardial infarction treatment.
引用
收藏
页码:1521 / 1526
页数:6
相关论文
共 34 条
[1]
Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes [J].
Ahlers, BA ;
Song, JL ;
Wang, JF ;
Zhang, XQ ;
Carl, LL ;
Tadros, GM ;
Rothblum, LI ;
Cheung, JY .
JOURNAL OF APPLIED PHYSIOLOGY, 2005, 98 (06) :2169-2176
[2]
Ai J, 2001, ACTA PHARMACOL SIN, V22, P512
[3]
Cardiac ionic currents and acute ischemia: From channels to arrhythmias [J].
Carmeliet, E .
PHYSIOLOGICAL REVIEWS, 1999, 79 (03) :917-1017
[4]
K+ currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts [J].
Chilton, L ;
Ohya, S ;
Freed, D ;
George, E ;
Drobic, V ;
Shibukawa, Y ;
MacCannell, KA ;
Imaizumi, Y ;
Clark, RB ;
Dixon, IMC ;
Giles, WR .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2005, 288 (06) :H2931-H2939
[5]
Increasing intracellular calcium of guinea pig ventricular myocytes induced by platelet activating factor through IP3 pathway [J].
Chu, WF ;
Sun, HL ;
Dong, DL ;
Qiao, GF ;
Yang, BF .
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 2006, 98 (01) :104-109
[6]
QUANTIFICATION OF ARRHYTHMIAS USING SCORING SYSTEMS - AN EXAMINATION OF 7 SCORES IN AN INVIVO MODEL OF REGIONAL MYOCARDIAL ISCHEMIA [J].
CURTIS, MJ ;
WALKER, MJA .
CARDIOVASCULAR RESEARCH, 1988, 22 (09) :656-665
[7]
The inward rectifier current (IK1) controls cardiac excitability and is involved in arrhythmogenesis [J].
Dhamoon, AS ;
Jalife, J .
HEART RHYTHM, 2005, 2 (03) :316-324
[8]
Selective inhibition of inward rectifier K+ channels (Kir2.1 or kir2.2) abolishes protection by ischemic preconditioning in rabbit ventricular cardiomyocytes [J].
Diaz, RJ ;
Zobel, C ;
Cho, HC ;
Batthish, M ;
Hinek, A ;
Backx, PH ;
Wilson, GJ .
CIRCULATION RESEARCH, 2004, 95 (03) :325-332
[9]
Differential expression of voltage-gated K+ channel genes in left ventricular remodeled myocardium after experimental myocardial infarction [J].
GidhJain, M ;
Huang, B ;
Jain, P ;
ElSherif, N .
CIRCULATION RESEARCH, 1996, 79 (04) :669-675
[10]
Spatial alterations of Kv channels expression and K+ currents in post-MI remodeled rat heart [J].
Huang, B ;
Qin, D ;
El-Sherif, N .
CARDIOVASCULAR RESEARCH, 2001, 52 (02) :246-254