Abstract：Objective: To investigate the effects of miR-425-5p on heart failure in rats and preliminarily explore its potential mechanism of action. Methods: A rat model of heart failure was established through multiple intraperitoneal injections of doxorubicin hydrochloride. After successful modeling, healthy male SD rats were randomly divided into five groups: model group, NC-Inhibitor group, miR-425-5p Inhibitor group, NC-agomir group, and miR-425-5p agomir group, with 10 rats in each group. An additional 10 healthy SD rats were used as the control group. After 4 weeks of intervention, cardiac function indicators including left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) were measured in each group. HE staining was used to observe morphological changes in myocardial tissue. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in myocardial tissue were determined by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) levels in myocardial tissue were detected by flow cytometry. qRT-PCR was used to detect the levels of miR-425-5p, ERK, and Nrf2 mRNA in myocardial tissue. Western Blot was performed to detect the protein levels of p-ERK and Nrf2. Results: Compared with the control group, rats in the model group showed significantly increased LVEDD, LVESD, and MDA levels, while LVEF, LVFS, SOD, GSH-Px, and ROS levels were significantly decreased. Pathological damage to myocardial tissue was increased, and miR-425-5p mRNA levels were significantly reduced. Additionally, ERK mRNA, Nrf2 mRNA, p-ERK, and Nrf2 protein expression levels were significantly decreased. Compared with the model group, rats in the miR-425-5p Inhibitor group exhibited further increases in LVEDD, LVESD, and MDA levels, with decreases in LVEF, LVFS, SOD, GSH-Px, and ROS levels. Pathological damage to myocardial tissue was exacerbated, and ERK mRNA, Nrf2 mRNA, p-ERK, and Nrf2 protein expression levels were significantly reduced. In contrast, rats in the miR-425-5p agomir group showed significant decreases in LVEDD, LVESD, and MDA levels, with increases in LVEF, LVFS, SOD, GSH-Px, and ROS levels. Pathological damage to myocardial tissue was alleviated, and ERK mRNA, Nrf2 mRNA, p-ERK, and Nrf2 protein expression levels were significantly increased. Conclusion: miR-425-5p inhibits heart failure in rats by regulating oxidative damage mediated by the ERK/Nrf2 signaling pathway.
2025, Vol. 31 
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