马钱苷元抗大鼠实验性心律失常的作用与机制预测  

Effect of Loganetin on Experimental Arrhythmia in Rats and Prediction of Its Mechanism

作　　者：冯群 李欣 姚景春 肖敏 赵涛 张贵民 FENG Qun;LI Xin;YAO Jing-chun;XIAO Min;ZHAO Tao;ZHANG Gui-min(Center for New Drug Safety Evaluation of Lunan Pharmaceutical Group Co.,Ltd.,State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Linyi 276006,China;Shandong New Time Pharmaceutical Co.,Ltd.,Linyi 273400,China)

机构地区：[1]鲁南制药集团股份有限公司新药安评中心,中药制药共性技术国家重点实验室,山东临沂276006 [2]山东新时代药业有限公司,山东临沂273400

出　　处：《现代中药研究与实践》2021年第2期30-33,共4页Research and Practice on Chinese Medicines

基　　金：山东省重大科技创新工程项目(2018CXGC1305)。

摘　　要：目的研究马钱苷元对大鼠实验性心律失常的保护作用,探索其作用靶点和机制。方法分别建立氯仿、乌头碱诱导大鼠实验性心律失常模型,各实验分为模型、马钱苷元低、高剂量(1 mg/kg、10 mg/kg)、胺碘酮4个组,预先给药3 d,末次给药后,分别给予氯仿、乌头碱,观察大鼠室颤发生情况、心律失常发生时间和持续时间。用AutoDock Vina软件,探索马钱苷元与心律失常靶点的亲和力和结合方式。结果马钱苷元10 mg/kg能明显降低氯仿所致大鼠的室颤发生率、延长乌头碱所致室早潜伏期并缩短持续时间,马钱苷元1 mg/kg无明显作用。马钱苷元与SCN5A和KCNH2均结合能力较好,结合形式以氢键为主。结论马钱苷元具有显著的抗心律失常作用,可能成为一种钠离子通道阻滞剂。Objective To study the protective effect of loganetin on experimental cardiac arrhythmia and explore the targets and potential mechanism.Methods Arrhythmia models are induced by chloroform and aconitine in rats.Rats are divided into four groups:model,loganetin(1 mg/kg and 10 mg/kg)and amiodarone.And they are pretreated with appropriate drugs for three days.After the last time of administration,rats are given chloroform and aconitine,respectively.The occurrence of ventricular fibrillation,the latent period and duration of premature ventricular contractions in rats are observed.Affinities and binding modes of the key proteins of arrhythmia with loganetin are verified by AutoDock Vina software.Results Compared with control group,occurrence rate of ventricular fibrillation with the administration of loganetin(10 mg/kg)is statistically reduced.Incubation period of premature ventricular contractions induced by aconitine in rats is delayed and duration is reduced dramatically.In the meanwhile,loganetin(1 mg/kg)shows no remarkable activities.The results of molecular docking show strong combining capacity between loganetin and SCN5A or KCNH2,which indicated that hydrogen bonding are the main forms of interaction.Conclusion Loganetin produce cardio-protective effects against arrhythmias,implying the potential probability to be a sodium channel blocking drug.

关 键 词：马钱苷元 心律失常 氯仿 乌头碱 分子对接 

分 类 号：R285.5[医药卫生—中药学]