Improvement of ventricular remodeling and regulation of PI3K/Akt/mTOR signaling pathway in rats with heart failure by polysaccharides from Stropharia rugosoannulata

MOLECULAR & CELLULAR TOXICOLOGY(2023)

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摘要
Background Heart failure is a syndrome of impaired cardiac circulation caused by the inability of the heart to provide adequate blood supply. Objective This study aimed to evaluate the improvement of ventricular remodeling and the regulation of PI3K/Akt/mTOR signaling pathway in rats with heart failure by polysaccharides from Stropharia rugosoannulata . Results In high dose group of polysaccharides from Stropharia rugosoannulata , the levels of LVESD, LVEDD, LVMI, CI, PVCA, CVF, and MMP-2 and MMP-9 mRNA expression in rats with heart failure were significantly decreased, while the levels of LVEF, LVFS were significantly elevated ( P <0.05). In high dose group of polysaccharides from Stropharia rugosoannulata , the levels of PI3K, p-Akt/Akt, p-mTOR/mTOR, and cleaved-caspase 3 expression and TIMP-1 mRNA expression were significantly elevated, while Bax, p65, Bcl2 protein expression and serum levels of PRA, AngII, ALD, IL-6, TNF-α, ST2 and NT-proBNP were significantly decreased ( P <0.05). Conclusions Polysaccharides from Stropharia rugosoannulata can improve ventricular remodeling and cardiac function, reduce inflammatory response and protect cardiac function in rats with heart failure in a dose-dependent manner, and the mechanism of action may be related to the regulation of MMPs/TIMPs balance, inhibition of RAAS system and activation of PI3K/Akt/mTOR signaling pathway.
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关键词
Heart failure,Polysaccharides from Stropharia rugosoannulata,Ventricular remodeling,Cardiac function,PI3K/Akt/mTOR signaling pathway
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