Effect of Leonurine on p38 MAPK Signaling Pathway and  miRNA-1 in Cardiomyocyte Hypertrophy Induced by AngⅡ

Li-na LU; Zhao-wen LIANG; Jian-hua LUO; Li LI; Lu YUAN; Hui YANG; Dong-hua YANG

doi:10.13422/j.cnki.syfjx.20190337

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Effect of Leonurine on p38 MAPK Signaling Pathway and miRNA-1 in Cardiomyocyte Hypertrophy Induced by AngⅡ

Pharmacology | 更新时间：2021-02-09

- Effect of Leonurine on p38 MAPK Signaling Pathway and miRNA-1 in Cardiomyocyte Hypertrophy Induced by AngⅡ
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 3, Pages: 81-86(2019)
- 作者机构：
  
  1.贵州省人民医院，贵阳　 550002
  2.贵阳中医学院　第二附属医院，贵阳　 550003
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190337
  CLC： R2-0;R22;R285.5
- Received：19 July 2018，
  
  Published Online：16 November 2018，
  
  Published：05 February 2019
- 稿件说明：
移动端阅览
Li-na LU, Zhao-wen LIANG, Jian-hua LUO, et al. Effect of Leonurine on p38 MAPK Signaling Pathway and miRNA-1 in Cardiomyocyte Hypertrophy Induced by AngⅡ[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(3): 81-86.
DOI：

Li-na LU, Zhao-wen LIANG, Jian-hua LUO, et al. Effect of Leonurine on p38 MAPK Signaling Pathway and miRNA-1 in Cardiomyocyte Hypertrophy Induced by AngⅡ[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(3): 81-86. DOI： 10.13422/j.cnki.syfjx.20190337.

摘要

目的:

研究益母草碱对血管紧张素Ⅱ(angiotensin

AngⅡ)诱导心肌细胞肥大的作用，并分析其对p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase

p38 MAPK)信号通路和微小RNA-1(microRNA-1，miRNA-1)表达的影响。

方法:

以AngⅡ(0.1 μmol·L

-1

)诱导肥大心肌细胞。实验分为空白组，模型组，p38 MAPK抑制剂组(SB203580，10 μmol·L

-1

)以及益母草碱低、中、高浓度组(5，10，20 μmol·L

-1

)。以图像分析软件测量心肌细胞表面积；Folin-酚试剂法(Lowry)检测心肌细胞蛋白含量；酶联免疫吸附测定法(enzyme-linked immunosorbent assay

ELISA)检测细胞上清心房钠尿肽(atrial natriuretic peptide

ANP)含量；实时荧光定量聚合酶链式反应(Real-time PCR)检测心肌细胞miRNA-1 mRNA的表达水平；蛋白免疫印迹法(Western blot)检测心肌细胞内皮素-1(endothelin-1，ET-1)，p38 MAPK，磷酸化p38 MAPK(p-p38 MAPK)，肌细胞增强因子2 (myocyte enhancer factor 2，MEF2)，

-肌球蛋白重链(

-myosin heavy chain

-MHC)和

-肌球蛋白重链(

-myosin heavy chain

-MHC)蛋白的表达水平。

结果:

与空白组比较，模型组心肌细胞表面积、蛋白含量及细胞上清ANP含量明显升高(

0.05)，ET-1，p38 MAPK

p-p38 MAPK

MEF2和

-MHC蛋白表达水平明显上调(

0.05)，

-MHC蛋白及miRNA-1 mRNA的表达水平明显下调(

0.05)。与模型组比较，益母草碱高浓度组明显减少肥大心肌细胞表面积、蛋白含量及细胞上清ANP含量(

0.05)；下调ET-1，p38 MAPK

p-p38 MAPK

MEF2和

-MHC蛋白表达水平(

0.05)；上调

-MHC蛋白及miRNA-1的表达水平(

0.05)。

结论:

益母草碱高浓度组(20 μmol·L

-1

)可抑制AngⅡ诱导的心肌细胞肥大，其机制可能与抑制p38 MAPK信号通路活化和上调miRNA-1的表达有关。

Abstract

Objective:

To investigate the inhibitory effect of leonurine on cardiomyocyte hypertrophy induced by angiotensin Ⅱ(Ang Ⅱ) and its effect on p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and miRNA-1.

Method:

Cardiomyocyte hypertrophy was induced by Ang Ⅱ (0.1 μmol·L

-1

) in primary neonatal cardiomyocytes. Experiments were designed in 6 groups as following: normal group

model group

p38 MAPK inhibitor group (SB203580

10 μmol·L

-1

)

low-dose(5 μmol·L

-1

)

middle-dose(10 μmol·L

-1

) and high-dose(20 μmol·L

-1

) group. The cardiomyocyte surface area was measured by image software

and the protein contents were detected by Lowry. The concentrations of ANP in the culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The expression level of miRNA-1 was detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR)

and the protein expression levels of endothelin-1 (ET-1)

p38 MAPK

p-p38 MAPK

myocyte enhancer factor 2 (MEF2)

-myosin heavy chain (

-MHC)

-myosin heavy chain (

-MHC) were detected by Western blot.

Result:

Compared with normal group

the surface area of cardiomyocyte

the protein contents

the concentrations of ANP

and the protein expression levels of ET-1

p38 MAPK

p-p38 MAPK

MEF2

-MHC in model group were higher (

0.05)

but the protein expression levels of

-MHC and miRNA-1 were lower than those in normal group (

0.05). Compared with model group

the surface area of cardiomyocyte

the protein contents

the concentrations of ANP

and the protein expression levels of ET-1

p38 MAPK

p-p38 MAPK

MEF2

-MHC in high-dose group were lower (

0.05)

but the protein expression levels of

-MHC and miRNA-1 were higher than those in model group (

0.05).

Conclusion:

Leonurine (20 μmol·L

-1

) could inhibit cardiomyocyte hypertrophy induced by AngⅡ

and the mechanism is related to the inhibition of activation of p38 MAPK signaling pathway and up-regulation the expression of miRNA-1.

关键词

Keywords

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