摘要
目的 本研究旨在分析马钱子碱(brucine)对分离的单个豚鼠心室肌细胞钠电流(INa+)的作用,并探索其抗心律失常的可能机制.方法 共选取24只健康的成年豚鼠作为实验对象,雌雄不拘,随机分为4组,每组6只:第1组是未接受任何处理的对照组,之后通过微量加样器使培养皿中brucine药物的终浓度分别达到3 μmol/L、10 μmol/L、30 μmol/L.采用急性酶解法分离获得单个豚鼠心室肌细胞,通过全细胞膜片钳技术测量离子通道电流,以检测不同浓度的brucine对豚鼠心室肌细胞INa+的影响.结果 正常的对照组没有明显的INa+电流峰值的变化,而brucine 3μmol/L组给药前后基本不影响INa+电流峰值,当brucine的浓度增加到10 μmol/L时,给药前后INa+电流峰值显著下降(P＜0.05),在30 μmol/L组给药前后INa+电流峰值大幅度减少(P＜0.01),并且这种抑制作用呈浓度依赖性.正常对照组及brucine 3 μmol/L剂量组中,电流-电压曲线(Ⅰ～Ⅴ曲线)并未受到显著的影响;然而,10 μmol/L、30μmol/L剂量组与对照组比较,INa+的Ⅰ～Ⅴ曲线上移,无平行移动,且曲线形状不变.结论 Brucine能够通过抑制心室肌细胞钠通道电流发挥抗心律失常作用.
Abstract
Objective To study the effects of brucine on sodium current(INa+)in isolated guinea pig ventricular myocytes and to explore its antiarrhythmic mechanism.Methods A total of 24 healthy guinea pigs were randomly di-vided into control group,brucine 3 μmol/L group,10 μmol/L group and 30 μmol/L group(n=6).To examine the effects of various levels of brucine on INa+of guinea pig ventricular myocytes,a singular ventricular cell was procured through enzymatic dissociation technique from healthy guinea pig hearts,followed by the implementation of the conven-tional whole cell patch clamp method.Results There was no significant change in the peak value of INa+current in the normal control group.The peak of INa+current was not affected before and after administration in the brucine 3 μmol/L group.The peak of INa+current was significantly decreased before and after administration in the brucine 10 μmol/L group(P＜0.05),The INa+current peak was significantly reduced before and after administration in the brucine 30μmol/L group(P＜0.01).Brucine can reduce the peak current INa+in a dose-dependent manner.From the current-volt-age curve(Ⅳ curve),it can be seen that the normal control group and the 3 μmol/L group have no effect at all.The 10μmol/L and 30 μmol/L groups are compared with the control group,and the Ⅳ curve of INa+was up-shifted without parallel movement and the shape of the curve does not change.Conclusion Brucine may exert anti-arrhythmia effects by inhibiting sodium channel currents.
基金项目
吉林省卫生健康委卫生健康科技能力提升项目(2019J100)
吉林省教育厅科技项目(十三五)(JJKH20201327KJ)
NETL
NSTL
万方数据