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

BACKGROUND

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.

METHODS

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 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.

RESULTS

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, 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.

CONCLUSION

Typhaneoside 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.