Qianyang Yuyin granule(潜阳育阴颗粒)modulates glycolysis and inflammatory response to treat hypertensive cardiac remodeling
摘要OBJECTIVE:To investigate the effect of Qianyang Yuyin granule(潜阳育阴颗粒QYYY)on Angll-induced hypertensive cardiac remodeling,focusing on the role of pyruvate kinase isozyme M2(PKM2)mediated glycolysis.METHODS:A hypertensive mouse model was established in male C57BL/6 mice by continuous infusion of angiotensin Ⅱ(Angll;1000 ng·kg-1·min-1).Mice were administered varying doses of QYYY,with sacubitril/valsartan(Sac/Val)serving as the positive control.Parameters evaluated included blood pressure,cardiac function,hypertrophy,fibrosis,inflammation,and apoptosis.The metabolic profile of myocardial tissue was analyzed using ultra performance liquid chromatography tandem mass spectrometry.Additionally,the involvement of the hypoxia-inducible factor 1-alpha(HIF-1α)/PKM2 signaling pathway was examined by Western blotting and immunohistochemistry.RESULTS:QYYY significantly lowered blood pressure,attenuated cardiac hypertrophy and fibrosis,reduced serum levels of inflammatory factors tumor necrosis factor-α and tumor necrosis factor-β,and decreased activation of phospho-NF-kappa B p65 pathway in cardiac tissue of hypertensive mice.Metabolomic analysis indicated that QYYY ameliorated cardiometabolic dysfunction,primarily associated with energy and amino acid metabolism,involving modulation of the HIF-1α/PKM2-mediated glycolytic pathway.CONCLUSION:QYYY effectively improves cardiac remodeling in hypertensive mice,potentially through inhibition of the PKM2-mediated glycolytic signaling pathway.
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