Eleutheroside B Ameliorates Cardiomyocytes Necroptosis in High-Altitude-Induced Myocardial Injury via Nrf2/HO-1 Signaling Pathway.

Abstract

This study was designed to evaluate the protective effects of eleutheroside B (EB) in high-altitude-induced myocardial injury (HAMI) and to unravel the underlying molecular mechanisms. SD rats were used for in vivo experiments. Following pretreatment with EB, the SD rats were exposed to a hypobaric environment within a hypobaric chamber for 48 h. Electrocardiograms, H&E staining, and serum biochemical indices were measured to evaluate the protective effects of EB on HAMI. Immunofluorescence and Western blotting were utilized to detect the expression of associated proteins. In parallel, a hypobaric hypoxic cell incubator was used to establish an in vitro model of hypobaric hypoxia-induced cell injury. The anti-necroptotic effect and its potential underlying mechanisms were investigated and verified in vitro. Exposure to hypobaric hypoxia led to electrocardiogram disorders, pathological changes in myocardial tissue, increased concentrations of BNP and CK-MB, and elevated levels of oxidative stress indicators and inflammatory factors. Additionally, the expression of necroptosis-related proteins was upregulated. Pretreatment with EB effectively ameliorated myocardial injury caused by hypobaric hypoxia, mitigated oxidative stress and inflammation, and suppressed necroptosis. Furthermore, EB facilitated the translocation of Nrf2 into the nucleus. In conclusion, this study provides evidence suggesting that EB may exert a protective effect against HAMI by inhibiting cardiomyocyte necroptosis via the Nrf2/HO-1 signaling pathway.