刺槐素干预阵发性心房颤动小鼠的量效及作用机制研究  

Mechanism of Acacetin in Treatment of Paroxysmal Atrial Fibrillation in Mice

作　　者：陈思静 徐耀 祁建勇 于娟 CHEN Sijing;XU Yao;QI Jianyong;YU Juan(The Second Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510006,Guangdong,China)

机构地区：[1]广州中医药大学第二临床医学院 [2]广东药科大学生命科学与生物制药学院 [3]广州中医药大学第二附属医院重症医学中医药应用研究团队 [4]广东省中医科学院公共实验室,广州510120

出　　处：《中西医结合心脑血管病杂志》2023年第13期2391-2395,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：广东省自然科学基金项目(No.2020A1515010777)。

摘　　要：目的:探讨不同剂量刺槐素对阵发性心房颤动小鼠的作用及其电生理机制。方法:动物实验中,将48只C57/BL6J小鼠随机分为空白组、模型组、胺碘酮组、刺槐素低剂量组(12 mg/kg)、刺槐素中剂量组(24 mg/kg)、刺槐素高剂量组(48 mg/kg),每组8只。连续给药3 d后,腹腔注射0.5 mg/kg盐酸异丙肾上腺素,1 min后给予电刺激(连续单刺激,电压0.08 V,频率90 Hz)21 min,测量并统计小鼠心房颤动发作总时间。细胞实验中,选取中国仓鼠卵巢细胞(CHO-K1),通过转染小鼠Kv1.5质粒,运用膜片钳全细胞记录技术,观察刺槐素对mKv1.5的作用。结果:动物实验发现,与空白组相比,模型组心房颤动持续时间明显延长(P<0.01);与模型组相比,刺槐素高剂量组、胺碘酮组心房颤动持续时间明显缩短(P<0.05)。刺槐素呈剂量依赖性抑制小鼠心房颤动发作,半数抑制浓度为4.235 mg/kg。细胞实验发现刺槐素可抑制中国仓鼠卵巢细胞Kv1.5通道的峰值电流幅度,并呈电压依赖性地抑制Kv1.5通道电流,对Kv1.5通道的电流稳态激活曲线门控机制无明显作用。结论:刺槐素呈剂量依赖性抑制小鼠心房颤动发作,其机制可能是阻断超快速延迟整流钾通道有关。Objective:To investigate the effects of different doses of Acacetin on mice with atrial fibrillation and its electrophysiological mechanism.Methods:Forty-eight C57/BL6J mice were randomly divided into 3 groups:blank group,model group,Amiodarone group,Acacetin low dose group(12 mg/kg),Acacetin medium dose group(24 mg/kg),and Acacetin high dose group(48 mg/kg),with 8 mice in each group.After 3 days of continuous treatment,0.5 mg/kg of isoprenaline hydrochloride was injected intraperitoneally,and electrical stimulation(continuous single stimulation,0.08 V,90 Hz)was given for 21 minute,and the total time of atrial fibrillation episodes in mice was measured and counted.Chinese hamster ovary cells were selected and transfected with mouse Kv1.5 plasmid,and the effect of Acacetin on mKv1.5 was observed by membrane clamp whole cell recording technique.Results:The duration of atrial fibrillation was significantly prolonged in model group compared with that in blank group(P<0.01),and the duration of atrial fibrillation was significantly shortened in Acacetin high dose group and the Amiodarone group compared with model group(P<0.05).The half-inhibitory concentration was 4.235 mg/kg.Cellular experiments revealed that Acacetin inhibited the peak current amplitude of Kv1.5 channels in Chinese hamster ovary cells and suppressed Kv1.5 channel currents in a voltage-dependent manner,without significant effect on the current steady-state activation curve gating mechanism of Kv1.5 channels.Conclusion:Acacetin inhibited paroxysmal atrial fibrillation in mice in a dose-dependent manner,and the mechanism may be related to the blockade of ultra rapid delayed rectifier potassium current.

关 键 词：心房颤动 刺槐素 超快速延迟整流钾通道 实验研究 

分 类 号：R285.5[医药卫生—中药学]