Effect of <italic style="font-style: italic">Guizhi Gancao</italic> Decoction （桂枝甘草汤） on IKs in Guinea Pig Ventricular Myocytes and IKr in HEK293 Cells

XING Zuoying; WANG Yongxia; ZHU Mingjun; HU Yucai; CHEN Zhaoqi; GAO Yuan; SONG Huanhuan; QIU Boyong

doi:10.13288/j.11-2166/r.2023.07.014

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Effect of Guizhi Gancao Decoction （桂枝甘草汤） on IKs in Guinea Pig Ventricular Myocytes and IKr in HEK293 Cells

更新时间：2023-04-17

- Effect of Guizhi Gancao Decoction （桂枝甘草汤） on IKs in Guinea Pig Ventricular Myocytes and IKr in HEK293 Cells
- Journal of Traditional Chinese Medicine Vol. 64, Issue 7, Pages: 729-735(2023)
- 作者机构：
  
  1.河南中医药大学，河南省郑州市金水区金水东路156号，450000
  2.河南中医药大学第一附属医院
  3.河南省人民医院/郑州大学人民医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2023.07.014
  CLC：
- Received：29 September 2022，
  
  Revised：2022-12-26，
  
  Published：02 April 2023
- 稿件说明：
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邢作英,王永霞,朱明军等.桂枝甘草汤对豚鼠心室肌细胞IKs及HEK293细胞IKr的影响[J].中医杂志,2023,64(07):729-735.

XING Zuoying,WANG Yongxia,ZHU Mingjun,et al.Effect of Guizhi Gancao Decoction （桂枝甘草汤） on IKs in Guinea Pig Ventricular Myocytes and IKr in HEK293 Cells[J].Journal of Traditional Chinese Medicine,2023,64(07):729-735.
邢作英,王永霞,朱明军等.桂枝甘草汤对豚鼠心室肌细胞IKs及HEK293细胞IKr的影响[J].中医杂志,2023,64(07):729-735. DOI： 10.13288/j.11-2166/r.2023.07.014.

XING Zuoying,WANG Yongxia,ZHU Mingjun,et al.Effect of Guizhi Gancao Decoction （桂枝甘草汤） on IKs in Guinea Pig Ventricular Myocytes and IKr in HEK293 Cells[J].Journal of Traditional Chinese Medicine,2023,64(07):729-735. DOI： 10.13288/j.11-2166/r.2023.07.014.

摘要

目的

探讨桂枝甘草汤治疗心律失常的可能作用机制及配伍意义。

方法

30只SD大鼠随机分为桂枝组（桂枝单煎液120 mg/ml）、甘草组（甘草单煎液60 mg/ml）、桂枝甘草单煎液混合组（桂枝单煎液+甘草单煎液混合180 mg/ml）、桂枝甘草汤同煎液组（桂枝和甘草同煎液180 mg/ml）、对照组（生理盐水），每组6只。各组每天灌胃相应药物1 ml/100 g，3天后腔静脉取血制备含药血清。分离豚鼠心室肌细胞，设桂枝血清组、甘草血清组、桂枝甘草单煎液混合血清组、桂枝甘草汤同煎液血清组、对照血清组，每组5个复孔；各组以体积比分别加入10%和15%浓度含药血清，培养24 h后分别检测各组在0、20、30、40、50 mV条件下慢激活延迟整流钾电流（IKs）电流密度。HEK293细胞分组及干预方法同心室肌细胞，培养24 h后分别检测各组在0、20、30、40、50 mV条件下快激活延迟整流钾电流（IKr）尾电流密度及IKr尾电流动力学参数（包括激活半电压、斜率因子）。

结果

在10%浓度药物干预下，0、20、30、40、50 mV时各组IKs电流密度比较差异均无统计学意义（

＞0.05），20、30、40、50 mV时各组IKr尾电流密度比较差异均无统计学意义（

＞0.05）。在15%浓度药物干预下，与对照血清组比较，甘草血清组和桂枝甘草单煎液混合血清组各电压IKs电流密度均降低，桂枝血清组30、40、50 mV时IKs电流密度降低，桂枝甘草汤同煎液血清组50 mV时IKs电流密度降低（

＜0.05）；桂枝甘草汤同煎液血清组各电压IKr尾电流密度均降低，桂枝甘草单煎液混合血清组50 mV时IKr尾电流密度降低，甘草血清组0 mV时IKr尾电流密度升高（

＜0.05）。在15%浓度药物干预下，与甘草血清组比较，桂枝甘草汤同煎液血清组30 mV时IKs电流密度升高，各电压IKr尾电流密度均降低（

＜0.05）；与桂枝血清组比较，桂枝甘草汤同煎液血清组30、40、50 mV时IKr尾电流密度降低（

＜0.05）。与对照血清组比较，在10%药物浓度干预下，各组IKr尾电流激活半电压均减小（

＜0.05）；在15%药物浓度干预下，各组IKr尾电流激活半电压均减小（

＜0.05），甘草血清组、桂枝血清组斜率因子减小（

＜0.05）。

结论

桂枝甘草汤可在一定程度上抑制心室肌细胞IKs及HEK293细胞IKr，这可能是其治疗心律失常的作用机制之一，且方中桂枝和甘草配伍具有协同增效的作用。

Abstract

Objective

To observe the possible mechanism in treating arrhythmia and the compatibility significance of

Guizhi Gancao Decoction

（GGD）.

Methods

A total of 30 SD rats were randomly divided into

Guizhi

（Ramulus Cinnamomi） group （

Guizhi Decoction

120 mg/ml），

Gancao

（Radix et Rhizoma Glycyrrhizae） group （

Gancao Decoction

60 mg/ml），

Guizhi

and

Gancao Decoction

mixed group （

Guizhi Decoction

Gancao Decoction

mixed 180 mg/ml）， GGD （

Guizhi

and

Gancao

boiling

Decoction

180 mg/ml）， and the control group （saline solution）， with each group of 6 rats. The rats were intragastrically given 1 ml/100 g corresponding decoction per day. After 3 days， the medicinal serum was prepared by taking the cavity venous blood. Guinea pigs' ventricular myocytes were separated in each of the five groups， with 5 duplicated wells for each group. Each group was added with 10% and 15% concentrations of medicinal serum respectively， and the current density of the slow activation delayed rectifier potassium current （IKs） of each group was detected under the conditions of 0， 20， 30， 40， and 50 mV after culturing 24 h， respectively. HEK293 cell grouping and intervention methods were the same with ventricular muscle cells. Tail current density and the rapid activation delayed rectifier potassium current （ IKr）， tail current including activating semi-voltage and slope factor of IKr were detected under the conditions of 0， 20， 30， 40， and 50 mV conditions.

Results

Under the intervention of 10% concentration of decoction， there was no statistical significance for all groups of both IKs and IKs current density and at 0， 20， 30， 40， and 50 mV （

＞0.05）. Under the intervention of 15% concentration of decoction， compared with the control group， the IKs voltage density of the

Gancao

serum group and

Guizhi Gancao Decoction

mixed group was reduced， and the IKs current density was reduced in the

Guizhi

serum group under 30， 40， and 50 mV. The IKs current density at 50 mV of the GGD co boiling group was decreased （

＜0.05）. The voltage IKr tail current density of the GGD co boiling group was reduced. The IKr tail current density of

Guizhi

and

Gancao

Decoction

mixed group at 50 mV decreased， and the IKr tail current density increased in the

Gancao

serum group under 0 mV （

＜0.05）. Under the 15% concentration of decoction， compared with the

Gancao

serum group， the current density of IKs of the GGD co boiling group at 30 mV increased， and under every each voltage IKr tail current density decreased （

＜0.05）. Compared with

Guizhi

serum soup， the current density of the IKr tail of the

Guizhi

and

Gancao

boiling serum group was decreased at 30， 40， and 50 mV （

＜0.05）. Compared with the control serum group， under the intervention of 10% decoction， the semi-voltage activation of IKr tail currents in all groups was reduced （

＜0.05）. Under the intervention of 15% concentration of decoction， the semi-voltage activation of IKr tail currents in all groups was reduced. （

＜0.05）， and the slope factors of the

Gancao

serum group and the

Guizhi

serum group were decreased （

＜0.05）.

Conclusions

GGD can inhibit IKS in the ventricular muscle cell and IKr in HEK293 cells to a certain extent. This may be one of the mechanisms of the decoction in treatment of arrhythmia， and the combination of

Guizhi

and

Gancao

in the formula has a synergistic effect.

关键词

Keywords

references

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Effect of Guizhi Gancao Decoction （桂枝甘草汤） on IKs in Guinea Pig Ventricular Myocytes and IKr in HEK293 Cells

DOI：10.13288/j.11-2166/r.2023.07.014

摘要

Abstract

关键词

Keywords

references