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Ginsenoside Rg2 Protects Heart After Acute Myocardial Infarction by Regulating PI3K/Akt/mTOR Signaling Pathway

  • role： Corresponding author, First author通信作者, 第一作者
  • Affiliation：

    School of Basic Medicine and Forensic Medicine，Henan University of Science and Technology， Luoyang 471000，China

  • Email：zjssir2004@sina.com.cn
  • Introduction：张希贤，从事临床医学研究，E-mail：zjssir2004@sina.com.cn
ZHANG Xixian1*,  
  • Affiliation：

    Henan University of Chinese Medicine，Zhengzhou 450046，China

SUN Junjie2,  
  • Affiliation：

    Henan University of Chinese Medicine，Zhengzhou 450046，China

LIU Qingya2

Resümee

ObjectiveTo investigate the cardioprotective effects of ginsenoside Rg2 in regulating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway following acute myocardial infarction （AMI） in rats.Methods（1） Cellular experiment： Cardiomyocytes were isolated from 24-hour-old Sprague-Dawley （SD） neonatal rats and subjected to primary culture. An in vitro model of cardiomyocytes under an ischemic-hypoxic microenvironment was established. Cardiomyocytes were pretreated with ginsenoside Rg2 （1， 2， 3 mg·L-1） for 4 hours， then placed in RPMI 1640 serum-free medium and cultured for 24 hours in a three-gas incubator （94% N2， 5% CO2， 1% O2）. The survival rate of cardiomyocytes was assessed using the methyl thiazolyl terazolium （MTT） assay. The levels of lactate dehydrogenase （LDH） leakage， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） activity， and malondialdehyde （MDA） content in the cell culture supernatant were measured using spectrophotometry. （2） Animal experiment： Specific-pathogen-free （SPF） SD rats were used to establish an AMI model using the Olivette method combined with previous studies. Rats that survived 24 hours post-surgery were randomly divided into a model group and ginsenoside Rg2 high-， medium-， and low-dose groups. The normal and model groups received normal saline， while the ginsenoside Rg2 groups were administered intragastrically at doses of 8， 4， and 2 mg·kg-1， once daily for 3 days. The levels of SOD， MDA， and GSH-Px in myocardial tissues were detected. Cardiomyocyte apoptosis was assessed using the TdT-mediated dUTP biotin nick end labeling （TUNEL） assay. The mRNA and protein expression levels of PI3K， Akt， mTOR， p62， nuclear factor-κB p65 （NF-κB p65）， and microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ in myocardial tissues were analyzed using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. Pathological changes in the infarct border zone were observed under a light microscope.Results（1） Cellular experiment： Compared with the normal group， the model group exhibited a significantly decreased cardiomyocyte survival rate， as well as reduced SOD and GSH-Px activity， whereas LDH activity and MDA content were significantly increased （P<0.05）. Compared with the model group， ginsenoside Rg2 intervention significantly increased cardiomyocyte survival， SOD activity， and GSH-Px activity， while reducing LDH activity and MDA content （P<0.05） in a dose-dependent manner. Pathological examination revealed that ginsenoside Rg2 alleviated infarct size， myocardial degeneration， and necrosis， while significantly reducing cardiomyocyte apoptosis. （2） Animal experiment： Compared with the normal group， the model group exhibited significantly lower SOD and GSH-Px activity （P<0.05） and higher MDA content （P<0.05） in myocardial tissues. Compared with the model group， all ginsenoside Rg2 groups showed significantly increased SOD and GSH-Px activity （P<0.05） and reduced MDA content （P<0.05）. Compared with the normal group， the model group exhibited significantly decreased mRNA and protein expression levels of PI3K， Akt， mTOR， p62，and LC3 Ⅱ/Ⅰ，whereas the expression levels of NF-κB p65 were significantly increased （P<0.05）. Compared with the model group， the ginsenoside Rg2 groups showed significantly increased PI3K， Akt， mTOR， and p62 expression， while NF-κB p65 expression levels were significantly decreased （P<0.05） in a dose-dependent manner，the mRNA and protein expression levels of LC3 Ⅱ/Ⅰ in ginsenoside Rg2 high-dose groups were significantly increased（P<0.05）.ConclusionGinsenoside Rg2 exerts cardioprotective effects following AMI in rats， potentially through the regulation of PI3K/Akt/mTOR-related protein expression.

Schlüsselwort

ginsenoside Rg2;myocardial infarction;phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway;autophagy;myocardial remodeling;cardiac protection

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