Astragaloside attenuates myocardial injury in a rat model of acute myocardial infarction by upregulating hypoxia inducible factor-1α and Notch1/Jagged1 signaling

Abstract

The present study aimed to investigate the mechanisms underlying the cardioprotective effect of Astragaloside against myocardial injury following myocardial infarction (MI) in a rat model. Male Wistar rats were subjected to left anterior descending branch ligation. The rats that survived 24 h (n=18) were randomly and equally assigned to three groups: MI model group, and 2.5 and 10 mg/kg/day Astragaloside group. A further six rats underwent identical surgical procedures without artery ligation, serving as sham controls. Following 28 days of treatment, the left ventricle was harvested for morphological analysis, and mRNA and protein expression levels of hypoxia inducible factor-1α (HIF-1α), Notch1 and Jagged1 were measured. Treatment with Astragaloside attenuated pathological changes in the myocardium. Compared with untreated MI rats, rats treated with Astragaloside exhibited significantly increased mRNA expression levels of HIF-1α, Notch1 and Jagged1 (all P<0.01). HIF-1α demonstrated a dose-dependent effect (P<0.05). Astragaloside (10 mg/kg/day) significantly increased HIF-1α (P<0.05), Notch1 (P<0.01) and Jagged1 (P<0.01) protein expression levels. Additionally, 2.5 mg/kg Astragaloside significantly increased Jagged1 protein expression levels compared with untreated MI rats. Furthermore, there was a dose-dependent effect of Astragaloside treatment (P<0.01). These findings suggested that the cardioprotective effects of Astragaloside against myocardial injury following MI may involve upregulation of HIF-α, Notch1 and Jagged1 signaling, implicating these molecules as therapeutic targets for the treatment of MI.