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目的观察小檗碱衍生物溴苄基四氢小檗碱(CPU86035)对豚鼠心室肌细胞钾离子流的影响,探讨其抗心律失常的离子通道机制。方法20只健康豚鼠,雌雄不拘,体重250-300 g,双酶法酶解获取单个豚鼠心室肌细胞,采取用药前后自身对照及全细胞膜片钳记录方法观察CPU86035 对正常豚鼠心室肌细胞快速激活延迟整流钾离子流(IKr)和缓慢激活延迟整流钾离子流(IKs)、内向整流钾离子流(IK1)的影响。结果CPU86035对豚鼠单个心室肌细胞快速激活(IKr)和缓慢激活延迟整流钾离子流(IKs)均呈浓度依赖性抑制作用,半数抑制浓度(ID50)分别为32μM和56 μM;CPU86035 对Ix1无明显影响。结论CPU86035对正常豚鼠心室肌细胞快速激活延迟整流钾离子流(Ikr)和缓慢激活延迟整流钾离子流(IKs)均有阻断作用,具有复合Ⅲ类抗心律失常药物的特点。
Objective To investigate the effect of berberine derivative bromobenzyl tetrahydropalberine (CPU86035) on potassium current in guinea pig ventricular myocytes and to explore its anti-arrhythmic ion channel mechanism. Methods Twenty healthy guinea pigs, male and female, weighing 250-300 g, were enrolled in the study. Single guinea pig ventricular myocytes were isolated by enzyme digestion. The self-control and whole-cell patch clamp recordings were used to observe the delayed activation of normal rat guinea pig ventricular myocytes Rectifier potassium current (IKr) and slowly activating delayed rectifier potassium currents (IKs) and inwardly rectifying potassium currents (IK1). Results CPU86035 inhibited Ikr and IKs in a concentration - dependent manner in a dose - dependent manner. The half maximal inhibitory concentration (ID50) were 32μM and 56 μM, respectively. CPU86035 had no obvious effect on Ix1 influences. Conclusion CPU86035 can block the rapid activation of delayed rectifier potassium current (Ikr) and slowly activate delayed rectifier potassium current (IKs) in normal guinea pig ventricular myocytes, and have the characteristics of compound Ⅲ antiarrhythmic drugs.