Journal of Jilin University(Medicine Edition) ›› 2021, Vol. 47 ›› Issue (4): 958-964.doi: 10.13481/j.1671-587X.20210419

• Research in basic medicine • Previous Articles     Next Articles

Inhibitory effect of diosmetin on myocardial hypertrophy induced by isoproterenol in mice and its mechanism

Pingli WANG1,Shenwei ZHANG2(),Jiang LI1   

  1. 1.Department of Surgery,Henan Medical College,Zhengzhou 451191,China
    2.Department of Cardiology
  • Received:2020-11-28 Online:2021-07-28 Published:2021-07-22
  • Contact: Shenwei ZHANG E-mail:zhangsw214@163.com

Abstract: Objective

To investigate the inhibitory effect of diosmetin (Dio) on isoprenaline (Iso)-induced myocardial hypertrophy in the mice, and to elucidate the biological mechanism.

Methods

Twenty-eight mice were randomly divided into control group, model group, low dose of Dio group, and high dose of Dio group. The mice in control group and model group were injected subcutaneously with normal saline or Iso (5 mg·kg-1·d-1) for 14 d, respectively. The mice in low dose and high dose of Dio groups were injected subcutaneously with Iso (5 mg·kg-1·d-1) for 14 d and intraperitoneally with Dio (5 and 20 mg·kg-1·d-1) for 14 d, respectively. After 14 d, the mice were sacrificed, the hearts and tibia were collected, the heart weights and left ventricular weights were weighed, the tibia lengths were measured, and the heart mass index and left ventricular mass index were calculated. The pathomorphology of left ventricular myocardium tissue was observed by HE, FITC-Lectin and Masson staining methods. The expression levels of α-myosin heavy chain (α-MHC) and β-myosin heavy chain (β-MHC) proteins in left ventricular myocardium tissue of the mice were detected by immunohistochemical method. The expression levels of extracellular regulated protein kinase 1/2 (ERK1/2), phosphorylated ERK1/2(p-ERK1/2),c-Jun N-terminal kinase 1/2 (JNK1/2), and phosphorylated JNK1/2(p-JNK1/2) proteins in left ventricular myocardium tissue of the mice were detected by Western blotting method.

Results

Compared with control group, the heart mass index and the left ventricular mass index of the mice in model group were significantly increased (P<0.01), the morphology of left ventricular myocardium tissue was significantly changed, the myocardial fibers were destructed with inflammatory cell infiltration, the cross-areas of myocardial cells were significantly enlarged (P<0.01),the microcirculatory perfusion of myocardium tissue was decreased, and the degree of interstitial fibrosis of myocardium tissue was increased (P<0.01); the expression level of α-MHC protein in the left ventricular myocardium tissue was significantly decreased (P<0.01), and the expression levels of β-MHC, p-ERK1/2 and p-JNK1/2 proteins were significantly increased(P<0.01). Compared with model group,the heart mass index and the left ventricular mass index in different doses of Dio groups were sifnificantly decreased(P<0.05 or P<0.01),the myocardial tissue injury was significantly reduced,the cross-areas of myocardial cells were significantly reduced (P<0.05 or P<0.01), the microcirculatory perfusion of myocardium tissue was enhanced,and the degree of interstitial fibrosis of myocardium tissue was significantly decreased (P<0.05 or P<0.01); the expression levels of α-MHC protein in the left ventricular myocardium tissue were significantly increased (P<0.05 or P<0.01), and the expression levels of β-MHC, p-ERK1/2 and p-JNK1/2 proteins were significantly decreased in a dose-dependent manner(P<0.05 or P<0.01).

Conclusion

Dio can improve Iso-induced myocardial hypertrophy in the mice, and its mechanism may be related to the inhibition of ERK1/2 and JNK1/2 signal pathways.

Key words: diosmetin, isoprenaline, myocardial hypertrophy, α-myosin heavy chain, β-myosin heary chain

CLC Number: 

  • R285.5