二甲双胍对自发性高血压大鼠心肌肥厚的改善作用及其机制

doi:10.13481/j.1671-587X.20260211

Abstract

Abstract:

Objective To discuss the ameliorative effect of metformin （Met） on myocardial hypertrophy in the spontaneously hypertensive rats （SHR）， and to clarify its possible mechanism of action. Methods The myocardial hypertrophy models were established with SHR， and the rats were randomly divided into SHR group and SHR+Met group； the age-matched male WKY rats were selected as WKY group. The rats in SHR+Met group were given Met suspension （300 mg·kg^-1·d^-1） by gavage for 6 weeks， and the rats in SHR group and WKY group were given equal volume of distilled water by gavage. After intervention， the body mass and left ventricular mass of the rats in various groups were measured， and the left ventricular mass index （LVMI） was calculated. Western blotting method was used to detect the expression levels of atrial natriuretic peptide （ANP） and brain natriuretic peptide （BNP） proteins in myocardium tissue of the rats in various groups； electron microscope was used to observe the mitochondrial ultrastructure of the cardiomyocytes of the rats in various groups； Western blotting method and real-time fluorescence quantitative PCR （RT-qPCR） method were used to detect the expression levels of mitochondrial fusion indicators optic atrophy 1 （OPA1） and mitofusin 2 （MFN2） proteins and mRNA in myocardium tissue of the rats in various groups. Results Compared with WKY group， the LVMI of the rats in SHR group was significantly increased （P<0.05）， and the expression levels of ANP and BNP proteins in myocardium tissue of the rats were significantly increased （P<0.05）. Compared with SHR group， the LVMI of the rats in SHR+Met group was significantly decreased （P<0.05）， and the expression levels of ANP and BNP proteins in myocardium tissue of the rats were significantly decreased （P<0.05）. The electron microscope results showed that in SHR group， the mitochondria in myocardium tissue of the rats were arranged disorderly， with widened， broken， or disappeared mitochondrial cristae spaces； in SHR+Met group， the mitochondrial morphology of the rats was partially restored， and the cristae remodeling was obvious. Compared with WKY group， the expression levels of OPA1 and MFN2 proteins and mRNA in myocardium tissue of the rats in SHR group were significantly decreased （P<0.05）； compared with SHR group， the levels of OPA1 and MFN2 proteins and mRNA in myocardium tissue of the rats in SHR+Met group were significantly increased （P<0.05）. Conclusion Met can alleviate myocardial hypertrophy in the SHR rats， and its mechanism may be related to improving mitochondrial morphology and up-regulating the expression of mitochondrial fusion proteins OPA1 and MFN2 in the myocardium tissue.

Key words: Myocardial hypertrophy, Metformin, Mitochondrial fusion, Optic atrophy 1, Mitofusin 2

CLC Number:

R329.28

Moujie LIU,Jing ZHANG,Huihui WU,Juhua XIE. Improvement effect of metformin on myocardial hypertrophy in spontaneously hypertensive rats and its mechanism[J].Journal of Jilin University(Medicine Edition), 2026, 52(2): 391-397.

Figures/Tables 5

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References 24

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Gene	Forward	Reverse
OPA1	5'-GTAGTGGTTGGGGTCCTTCC-3'	5'-AAGCTCTGTGTATTGAGTGCAGC-3'
MFN2	5'-ATGCCACCCTTGCCACAG-3'	5'-TCCTCCGACCACGAGAAT-3'
GAPDH	5'-ACAGCAACAGGGTGGTGGAC-3'	5'-TTTGAGGGTGCAGCGAACTT-3'

Group	Body weight（m/g）	LVM（m/g）	LVMI（η/%）
WKY	293.70±20.64	0.67±0.08	0.23±0.01
SHR	283.20±18.80	0.79±0.05	0.28±0.01^*
SHR+Met	272.00±18.54	0.66±0.11	0.24±0.03^△

Improvement effect of metformin on myocardial hypertrophy in spontaneously hypertensive rats and its mechanism

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