FOLLOWUS
Suxiao Jiuxin Pills Prevent Ventricular Fibrillation from Inhibiting L-type Calcium Currents CaV1.2
in vivo andin vitro - Chinese Journal of Integrative Medicine Vol. 29, Issue 2, Pages: 108-119(2023)
- Affiliations：
1.Acute Myocardial Infarction Key Laboratory of Chinese Medicine in Guangzhou, the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, Guangzhou (510006), China
2.Intensive Care Research Team of Traditional Chinese Medicine, the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, Guangzhou(510006), China
3.Animal Center, the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, Guangdong Province Academy of Chinese Medicine, Guangzhou (510006), China
- Author bio：
Prof. ZHANG Min-zhou, E-mail:mingzhouzhang8@163.com
- Funds：
DOI：10.1007/s11655-022-3623-7
CLC：Published：2023-02，
Published Online：03 November 2022，
Accepted：11 July 2022
Scan for full text
QI Jian-yong, KANG Dong-yuan, YU Juan, et al. Suxiao Jiuxin Pills Prevent Ventricular Fibrillation from Inhibiting L-type Calcium Currents CaV1.2
in vivo andin vitro . [J]. Chinese Journal of Integrative Medicine 29(2):108-119(2023)QI Jian-yong, KANG Dong-yuan, YU Juan, et al. Suxiao Jiuxin Pills Prevent Ventricular Fibrillation from Inhibiting L-type Calcium Currents CaV1.2
in vivo andin vitro . [J]. Chinese Journal of Integrative Medicine 29(2):108-119(2023) DOI： 10.1007/s11655-022-3623-7.
摘要
目的:
2
研究复方中药速效救心丸 (SJP)
是否是一种有效的、预防心室颤动 (VF) 的药物.
方法:
2
在新西兰兔和C57/BL6J小鼠体内
腹腔注射异丙肾上腺素 (ISO) 结合心电起搏
诱发心室颤动. 膜片钳实验
检测SJP对细胞L型钙通道电流 (CaV1.2) 、电压依赖性钠通道电流 (I
Na
) 、快速型和缓慢型延迟整流钾通道 (I
Kr
I
Ks
) 电流的作用. 计算机仿真实验
将SJP对CaV1.2电流影响的实验数据
整合入心室肌细胞动作电位 (AP) 模型和仿真心电图 (pseudo-ECG) 模型中.
结果:
2
SJP显著降低新西兰兔和C57/BL6J小鼠心室颤动发生的概率和室颤持续时间. 膜片钳实验显示SJP降低了CaV1.2通道的峰值电流幅度
半数有效抑制浓度 (IC
50
) 为16.9 mg/L. SJP-30 mg/L
-32.8±6.1 pA; 维拉帕米
-16.2±1.8 pA; 对照组
-234.5±16.7 pA
P
<
0.01) . CaV1.2通道电流的稳态激活曲线、失活曲线和复活曲线未发生显著变化. 进一步发现
SJP并未显著改变INa、IKr和IKs电流 (SJP与各自对照组相比
P
>
0.05) . 计算机仿真实验显示
SJP
减少CaV1.2电流
缩短动作电位时间
从而引起仿真心电图中室颤转变为窦性心律.
结论:
2
通过体内实验、体外实验、和计算机仿真实验证实
SJP通过抑制L-型钙通道CaV1.2电流
抑制室颤
为速效救心丸临床应用防治心室颤动
提供了实验基础.
Abstract
Objective:
2
To investigate whether Suxiao Jiuxin Pills (SJP)
a Chinese herbal remedy
is an anti-ventricular fibrillation (VF) agent.
Methods:
2
VF was induced by isoproterenolol (ISO) intraperitoneal injection followed by electrical pacing in mice and rabbits. The effects of SJP on the L-type calcium channel current (CaV1.2)
voltage-dependent sodium channel current (I
Na
)
rapid and slow delayed rectifier potassium channel current (I
Kr
and I
Ks
respectively) were studied by whole-cell patch-clamp method. Computer simulation was implemented to incorporate the experimental data of SJP effects on the CaV1.2 current into the action potential (AP) and pseudo-electrocardiography (pseudo-ECG) models.
Results:
2
SJP prevented VF induction and reduced VF durations significantly in mice and rabbits. Patch-clamp experiments revealed that SJP decreased the peak amplitude of the CaV1.2 current with a half maximal concentration (IC
50
) value of 16.9 mg/L (SJP-30 mg/L
–32.8±6.1 pA; Verapamil
–16.2±1.8 pA;
vs
. control
–234.5±16.7 pA
P
<
0.01
respectively). The steady-state activation curve
inactivation curve
and the recovery from inactivation of the CaV1.2 current were not shifted significantly. Specifically
SJP did not altered I
Na
I
Kr
and I
Ks
currents significantly (SJP
vs
. control
P
>
0.05). Computer simulation showed that SJP-reduced CaV1.2 current shortened the AP duration
transiting VF into sinus rhythm in pseudo-ECG.
Conclusion:
2
SJP reduced VF via inhibiting the CaV1.2 current with
in vivo
in vitro
and
in silico
studies
which provide experimental basis for SJP anti-VF clinical application.
关键词
速效救心丸心室颤动膜片钳计算机仿真CaV1.2钙通道
Keywords
Suxiao Jiuxin Pillsventricular fibrillationpatch clampsimulationCaV1.2
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