低钾状态下泮托拉唑致小鼠缓慢型心律失常

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (1): 73-77.

低钾状态下泮托拉唑致小鼠缓慢型心律失常

李帅¹, 朱文根¹, 阎霞², 赖玮¹, 俞建华¹, 万蓉², 洪葵^1,2,3*

1.南昌大学第二附属医院心血管内科, 江西南昌 330006;
2.南昌大学第二附属医院江西省分子医学重点实验室, 江西南昌 330006;
3.南昌大学第二附属医院医学遗传专科, 江西南昌 330006

收稿日期:2019-01-21 修回日期:2019-06-04 出版日期:2020-01-05 发布日期:2019-12-27
通讯作者: ^*hongkui88@163.com
基金资助:
江西省科技厅自然基金重点项目(210171ACB20033);江西省科技厅社会发展领域(20151BBB70266);江西省研究生创新专项资金(YC2016-B022)

Pantoprazole induces bradyarrhythmia in mice with hypokalemia

LI Shuai¹, ZHU Wen-gen¹, YAN Xia², LAI Wei¹, YU Jian-hua¹, WAN Rong², HONG Kui^1,2,3*

1. Department of Cardiovascular Medicine;
2. Jiangxi Provincial Key Laboratory of Molecular Medicine;
3. Department of Medical Genetics, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China

Received:2019-01-21 Revised:2019-06-04 Online:2020-01-05 Published:2019-12-27
Contact: ^*hongkui88@163.com

摘要/Abstract

摘要： 目的探讨低钾状态下泮托拉唑(PPZ)致小鼠心律失常的机制。方法将小鼠随机分为4组:对照组、PPZ组[20 mg/(kg·d),腹腔注射5周]、低钾组[FS组,用呋塞米(FS)复制小鼠低钾模型]和低钾泮托拉唑组(FS+PPZ组),每组各20只。第5周末监测各组小鼠心电参数(HR、PR间期、QRS间期和QTc间期)和自发性心律失常的发生。荧光定量PCR和Western blot检测超级化激活环核苷酸门控阳离子通道2和4(HCN2和HCN4)、电压门控性Na⁺通道α亚基(SCN5A)、L型Ca²⁺通道α1C亚基(CACNA1C)及T型Ca²⁺通道α1G亚基(CACNA1G)mRNA和蛋白表达。结果与对照组比较,PPZ组HR降低和PR间期延长(P＜0.01和P＜0.05);与FS组比较,FS+PPZ组HR和PR间期均进一步降低和延长(P＜0.01和P＜0.05),有4只小鼠出现窦性停搏(P＜0.05)。PPZ组较对照组HCN4 mRNA和蛋白水平均表达下降(P＜0.01),FS+PPZ组较FS组进一步降低(均P＜0.01);PPZ组较对照组HCN2仅mRNA水平表达下降(P＜0.05),FS+PPZ组较FS组进一步降低(P＜0.01)。结论在低钾状态下泮托拉唑可导致小鼠缓慢型心律失常,可能与HCN2和HCN4基因表达异常有关。

关键词: 泮托拉唑, 低钾血症, 心律失常, 机制

Abstract: Objective To investigate the mechanism of arrhythmia induced by pantoprazole (PPZ) in mice with hypokalemia. Methods Mice were randomly divided into control group, PPZ group [20 mg/(kg·d), intraperitoneal injection for 5 weeks], furosemide (FS) group and FS+PPZ group. After 5 weeks, the ECG parameters (heart rate, PR interval, QRS interval, QTc interval) and spontaneous arrhythmia were monitored. The changes of the mRNA and protein expression of hyperpolarization-activated and cyclic nucleotide-cation channels 2 and 4 (HCN2 and HCN4), cardiac voltage-gated sodium channel alpha subunit (SCN5A), L-type calcium channel alpha subunit (CACNA1C) and T-type calcium channel alpha subunit (CACNA1G) were analysed by real-time fluorescence quantitative PCR and Western blot technology. Results Compared with control group, the HR was significantly decreased and PR interval was prolonged in PPZ group (P＜0.01, P＜0.05). Compared with FS group,the HR and PR interval in FS+PPZ group were further decreased and prolonged (P＜0.01, P＜0.05), and 4 mice developed sinus arrest (SA) (P＜0.05). The expressions of HCN4 mRNA and protein in PPZ group were lower than those in control group (P＜0.01), respectively, and the expression in FS+PPZ group was lower than those in FS group (P＜0.01). The expression of HCN2 mRNA in PPZ group was lower than that in control group(P＜0.05), which was further decreased in FS+PPZ group compared with FS group (P＜0.01). Conclusions It is found that pantoprazole may lead to bradyarrhythmia in mice under hypokalemia, which may be related to abnormal expression of HCN2 and HCN4.

Key words: pantoprazole, hypokalemia, arrhythmia, mechanism

中图分类号:

R541.7

李帅, 朱文根, 阎霞, 赖玮, 俞建华, 万蓉, 洪葵. 低钾状态下泮托拉唑致小鼠缓慢型心律失常[J]. 基础医学与临床, 2020, 40(1): 73-77.

LI Shuai, ZHU Wen-gen, YAN Xia, LAI Wei, YU Jian-hua, WAN Rong, HONG Kui. Pantoprazole induces bradyarrhythmia in mice with hypokalemia[J]. Basic & Clinical Medicine, 2020, 40(1): 73-77.

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