Rg1在体外对乌头碱具有增效（强心）减毒（心脏毒）作用

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Rg1在体外对乌头碱具有增效（强心）减毒（心脏毒）作用

Original Article | Updated：2022-07-20

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- Rg1在体外对乌头碱具有增效（强心）减毒（心脏毒）作用
- Ginsenoside Rg₁ Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro
- Chinese Journal of Integrative Medicine 2022年28卷第8期页码：693-701
- Affiliations：
  
  1.State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School of Chengdu University of Traditional Chinese Medicine, Chengdu (611137), China
  2.Department of Pharmacy, Sichuan Veterans' Hospital, Chengdu (611236), China
- Author bio：
  
  Prof. PENG Cheng, E-mail:cdtcmpengcheng@126.com
- Funds：
  
  the National Natural Science Foundation of China(Nos. 81630101 and 81891012);Department of Science and Technology of Sichuan Province(2018JZ0081);the Open Research Fund of Chengdu University of Traditional Chinese Medicine Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China(2020XSGG001);Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province(20ZYKJCX0006)
- DOI：10.1007/s11655-022-3509-0
  中图分类号：
- 纸质出版日期：2022-08，
  
  网络出版日期：2022-06-20，
  
  录用日期：2021-01-06
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Xin XU, Xiao-fang XIE, Yan-hong DONG, 等. Rg1在体外对乌头碱具有增效（强心）减毒（心脏毒）作用[J]. Chinese Journal of Integrative Medicine, 2022,28(8):693-701.

Xin XU, Xiao-fang XIE, Yan-hong DONG, et al. Ginsenoside Rg₁ Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro[J]. Chinese Journal of Integrative Medicine, 2022,28(8):693-701.
Xin XU, Xiao-fang XIE, Yan-hong DONG, 等. Rg1在体外对乌头碱具有增效（强心）减毒（心脏毒）作用[J]. Chinese Journal of Integrative Medicine, 2022,28(8):693-701. DOI： 10.1007/s11655-022-3509-0.

Xin XU, Xiao-fang XIE, Yan-hong DONG, et al. Ginsenoside Rg₁ Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro[J]. Chinese Journal of Integrative Medicine, 2022,28(8):693-701. DOI： 10.1007/s11655-022-3509-0.

摘要

目的:

2

探讨人参皂苷Rg1 (Rg1) 和乌头碱 (AC) 对乳鼠心肌细胞 (NRCMs) 和戊巴比妥钠 (PS) 诱导的受损NRCMs的协同作用机制.

方法:

2

药物暴露1h后

用MTT法分别筛选出AC的毒性、无毒性和有效剂量

及Rg1对正常和受损NRCMs的最适配伍浓度. 然后

筛选出的不同浓度的AC单独或与Rg1配伍

与正常或受损的NRCMs 共同孵育1小时

观察细胞活性、细胞超微结构、凋亡、酸性磷酸酶 (ACP) 和乳酸脱氢酶 (LDH) 水平、细胞内钠离子[Na

+

]、钾离子[K

+

]和钙离子[Ca

2+

]水平以及Nav1.5、Kv4.2和RyR2基因的表达.

结果:

2

对于正常NRCMs

3000μmol/L AC显著抑制细胞活力 (

P

<

0.01)

促进细胞凋亡

破坏细胞结构 (

P

<

0.05)

低于3000μmol/L的低剂量AC和AC与Rg1的配伍对NRCMs的毒性较小. 与AC单独作用于NRCMs比较

3000μmol/L和10μmol/L AC与1μmol/L Rg1配伍显著降低细胞内Ca

2+

水平 (

P

<

0.01和

P

<

0.05)

3000μmol/L AC与1μmol/L Rg1配伍通过调节Nav1.5和RyR2表达显著降低细胞内Ca

2+

水平 (

P

<

0.01) . 对于受损NRCMs

1500μmol/L AC加重了细胞损伤 (

P

<

0.01)

0.1μmol/L和0.001μmol/L AC对受损NRCMs具有一定的保护作用. 与AC单独作用比较

Rg1与AC的配伍减少了细胞损伤

0.1μmol/L AC与1μmol/L Rg1配伍显著抑制细胞内Na

+

水平 (

P

<

0.05)

1500μmol/L AC与1μmol/L Rg1配伍通过调节受损NRCMs中Nav1.5、Kv4.2、RyR2的表达显著抑制细胞内K+水平 (

P

<

0.01) .

结论:

2

Rg1通过调节[Na

+

]、[K

+

]和[Ca

2+

]离子通道

抑制了AC的心脏毒性

增强了AC的强心作用.

Abstract

Objective:

2

To explore the synergic mechanism of ginsenoside Rg1 (Rg

1

) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs.

Methods:

2

The toxic

non-toxic

and effective doses of AC and the most suitable compatibility concentration of Rg1 for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4

5)-dimethylthiahiazo (-z-y1)-3

5-diphenytetrazoliumromide

respectively. Then

normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg1 for 1 h

and the cellular activity

cellular ultrastructure

apoptosis

leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH)

intracellular sodium ions [Na

+

]

potassium ions [K

+

] and calcium ions [Ca

2+

] levels

and Nav1.5

Kv4.2

and RyR

2

genes expressions in each group were examined.

Results:

2

For normal NRCMs

3000 μmol/L AC significantly inhibited cell viability (

P

<

0.01)

promoted cell apoptosis

and damaged cell structures (

P

<

0.05)

while other doses of AC lower than 3000 μmol/L and the combinations of AC and Rg

1

had little toxicity on NRCMs. Compared with AC acting on NRCMs alone

the co-treatment of 3000 and 10 μmol/L AC with 1 μmol/L Rg

1

significantly decreased the level of intracellular Ca

2+

(

P

<

0.01 or

P

<

0.05)

and the co-treatment of 3000 μmol/L AC with 1 μmol/L Rg

1

significantly decreased the level of intracellular Ca

2+

via regulating Nav1.5

RyR

2

expression (

P

<

0.01). For damaged NRCMs

1500 μmol/L AC aggravated cell damage (

P

<

0.01)

and 0.1 and 0.001 μmol/L AC showed moderate protective effect. Compared with AC used alone

the co-treatment of Rg

1

with AC reduced the cell damage

0.1 μmol/L AC with 1 μmol/L Rg

1

significantly inhibited the level of intracellular Na

+

(

P

<

0.05)

1500 μmol/L AC with 1 μmol/L Rg

1

significantly inhibited the level of intracellular K

+

(

P

<

0.01) via regulating Nav1.5

Kv4.2

RyR

2

expressions in impaired NRCMs.

Conclusion:

2

Rg

1

inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na

+

]

[K

+

]

and [Ca

2+

].

关键词

Keywords

aconitineginsenoside Rg1compatibilityion channel pathwaycardiomyocytes

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