Effect of typhaneoside on ventricular remodeling and regulation of PI3K/Akt/mTOR pathway.

X. Zhang,K. Yang,Y. Zhao,H. Zhang,W. Dong,W. Peng

doi:10.1007/s00059-019-4819-2

Abstract

BackgroundThis study aimed to investigate the effect of typhaneoside on ventricular remodeling and regulation of the PI3K/Akt/mTOR autophagy transduction pathway in rats with heart failure after myocardial infarction.MethodsThe effects of typhaneoside on the general condition of rats were observed in vivo using a rat model of heart failure after myocardial infarction had been established. The expression of serum N‑terminal pro-brain natriuretic peptide (NT-proBNP), matrix lysin 2 (ST2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected via ELISA. A hypoxia/reoxygenation model was established to analyze the number and morphology of autophagosomes in vitro by transmission electron microscopy. Light chain 3 (LC3) variations were detected by immunofluorescence. Western blotting was used to assess LC3-II/LC3-I and p62 expression as well as p‑Akt/Akt, p‑mTOR/mTOR ratios.ResultsCompared with the sham group, the general condition scores of the rats in the model group decreased significantly, while the expression of serum NT-proBNP, ST2, IL-6, TNF-α, MMP-2, and MMP-9 increased. The number of autophagosomes in the drug-containing serum group was significantly reduced and the ratio of LC3-II/LC3-I was significantly decreased. The expression of P62 protein was increased, and the ratios of p‑Akt/Akt and p‑mTOR/mTOR were significantly increased.ConclusionTyphaneoside regulates IL-6 and TNF-α as well as MMP-2 and MMP-9 in rats with heart failure after myocardial infarction. Typhaneoside can improve cardiac morphological structure and myocardial remodeling and enhance heart function. It may mediate autophagy inhibition in the cardiomyocyte anoxia/reoxygenation (A/R) pathway through the PI3K/Akt/mTOR autophagy transduction pathway.

Highlights

This study aimed to investigate the effect of typhaneoside on ventricular remodeling and regulation of the PI3K/Akt/mTOR autophagy transduction pathway in rats with heart failure after myocardial infarction
Compared with the RA group, the ratio of p-mTOR/ mTOR in the RA + drug + A/R group decreased significantly, indicating that drug serum (DS) could not reactivate mTOR proteins after RA inhibited mTOR. These results showed that RA can block the autophagy inhibition of DS during the cardiomyocyte hypoxia/reoxygenation /R process, which indicates that the drug-containing serum inhibits autophagy through the mTOR pathway
Typhaneoside can improve the morphological structure of the heart in a rat model of heart failure (HF) after myocardial infarction, can improve cardiac function indexes, and can improve myocardial remodeling, which may be related to the reduction of inflammatory factors and myocardial matrix metalloproteinase levels

Summary

Introduction

This study aimed to investigate the effect of typhaneoside on ventricular remodeling and regulation of the PI3K/Akt/mTOR autophagy transduction pathway in rats with heart failure after myocardial infarction. The effects of typhaneoside on the general condition of rats were observed in vivo using a rat model of heart failure after myocardial infarction had been established. The expression of serum N-terminal probrain natriuretic peptide (NT-proBNP), matrix lysin 2 (ST2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected via ELISA. Western blotting was used to assess LC3-II/LC3-I and p62 expression as well as p-Akt/Akt, p-mTOR/mTOR ratios. Compared with the sham group, the general condition scores of the rats in the model group decreased significantly, while the expression of serum NT-proBNP, ST2, IL-6, TNFα, MMP-2, and MMP-9 increased. The number of autophagosomes in the drug-containing serum group was significantly reduced and the ratio of LC3-II/LC3-I was significantly decreased. The expression of P62 protein was increased, and the ratios of p-Akt/Akt and p-mTOR/mTOR were significantly increased

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Discussion

Conclusion