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Ca^2+通道α1C亚基(CACNA1C)及T型Ca^2+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。
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(SCN5 A), L-type calcium channel alpha subunit(CACNA1 C) and T-type calcium channel alpha subunit(CACNA1 G) 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). ConclusionsIt is found that pantoprazole may lead to bradyarrhythmia in mice under hypokalemia, which may be related to abnormal expression of HCN2 and HCN4.
作者
李帅
朱文根
阎霞
赖玮
俞建华
万蓉
洪葵
LI Shuai;ZHU Wen-gen;YAN Xia;LAI Wei;YU Jian-hua;WAN Rong;HONG Kui(Department of Cardiovascular Medicine,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,China;Jiangxi Provincial Key Laboratory of Molecular Medicine,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,China;Department of Medical Genetics,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,China)
出处
《基础医学与临床》
CSCD
2020年第1期73-77,共5页
Basic and Clinical Medicine
基金
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)
