Journal of Jilin University(Medicine Edition) ›› 2021, Vol. 47 ›› Issue (6): 1437-1445.doi: 10.13481/j.1671-587X.20210613

• Research in basic medicine • Previous Articles     Next Articles

Protective effect of astragaloside Ⅳ on heart failure induced by over-expression of miRNA-1 and its mechanism

Yue HUANG1,Qiuning WANG2,Xuefeng YANG2,Guizhou TAO1()   

  1. 1.Department of Cardiology,First Affiliated Hospital,Jinzhou Medical University,Jinzhou 121000,China
    2.Department of Physiology,School of Basic Medical Sciences,Jinzhou Medical University,Jinzhou 121000,China
  • Received:2021-04-13 Online:2021-11-28 Published:2021-12-14
  • Contact: Guizhou TAO E-mail:tgz56789@163.com

Abstract: Objective

To study the protective effect of astragaloside Ⅳ (ASⅣ) on the heart failure(HF) induced by over-expression of microRNA-1 (miRNA-1) in the rats, and to clarify the possible mechanism.

Methods

A total of 32 SD rats were randomly divided into normal control group,miRNA-1 mimics negative virus control(miRNA-1 mimics NC) group,miRNA-1 mimics group,and ASⅣ+miRNA-1 mimics group,and there were 8 rats in each group. The HF models of rats were established by injecting miRNA-1 lentivirus in left ventricular wall. Real-time fluorescence quantitative PCR(RT-qPCR) method was used to detect the expression level of miRNA-1 in myocardium tissue of the rats in various groups, and echocardiography was used to examine the left ventricular injection fraction(EF) and left ventricular fraction shortening (FS) of the rats in various groups.The H9C2 cardiomyocytes were divided into normal control group, miRNA-1 mimics negative virus control(miRNA-1 mimics NC) group, miRNA-1 mimics group and ASⅣ+miRNA-1 mimics group. The H9C2 cardiomyocytes were infected with miRNA-1 lentivirus.RT-qPCR method was used to detect the expression levels of miRNA-1 in the H9C2 cardiomyocytes in various groups,and the survival rates of the H9C2 cardiomyocytes in various groups were detected by MTT method to screen the optimal concentration of ASⅣ.The calcium test box was used to detect the expression levels of calcium ions (Ca2+) in the H9C2 cardiomyocytes in various groups,RT-qPCR method was used to detect the expression levels of calcium/calmodulin dependent protein kinaseⅡ(CaMKⅡ)and ryanodine receptor type 2(RyR2)mRNA in the H9C2 cardiomyocytes in various groups,and Western blotting method was used to detect the expression levels of CamKⅡ and RyR2 proteins in the H9C2 cardiomyocytes in various groups.

Results

Compared with normal control group and miRNA-1 mimics NC group, the expression level of miRNA-1 in myocardium tissue of the rats in miRNA-1 mimics group was increased significantly (P<0.01),and the EF and FS were decreased significantly (P<0.01); compared with miRNA-1 mimics group, the expression level of miRNA-1 in myocardium tissue of the rats in ASⅣ+miRNA-1 mimics group was decreased significantly (P<0.01),and the EF and FS were increased significantly (P<0.01).Compared with normal control group and miRNA-1 mimics NC group, the expression level of miRNA-1 and Ca2+ level in the H9C2 cardiomyocytes of the rats in miRNA-1 mimics group were increased significantly (P<0.01), the expression levels of CaMKⅡ mRNA and protein were increased significantly (P<0.01),and the expression levels of RyR2 mRNA and protein were decreased significantly (P<0.01);compared with miRNA-1 mimics group, the expression levels of miRNA-1,Ca2+ level and the expression levels of CamKⅡ mRNA and protein in the H9C2 cardiomyocytes of the rats in ASⅣ+miRNA-1 mimics group were decreased significantly (P<0.01),and the expression levels of RyR2 mRNA and protein were increased significantly (P<0.01).

Conclusion

ASⅣ may be involved in the regulation of Ca2+ level in the cardiomyocytes by down-regulation of the expression of miRNA-1, thus improves the HF and plays a protective role in the heart.

Key words: astragalosideⅣ, microRNA -1, heart failure, calcium ion, ryanodine receptor type 2

CLC Number: 

  • R285.5