Abstract
PURPOSE: This study investigated the cardioprotective effects of an eight-week aerobic exercise program on cardiac histological and stereological parameters in rats with type 2 diabetes mellitus (T2DM), with a focus on structural remodeling and tissue composition. METHODS: Thirty-two male Wistar rats were randomly assigned to four groups: diabetic exercise (Dia + Exe), healthy exercise (Heal + Exe), diabetic control (Dia + Con), and healthy control (Heal + Con) groups. T2DM was induced via a high-fat diet combined with a low-dose streptozotocin injection. The aerobic exercise protocol involved progressive treadmill training five days per week for eight weeks. Stereological analysis, which is based on systematic uniform random sampling, was conducted to assess cardiac dimensions, tissue composition, and myocyte morphology. Histological evaluation was performed via hematoxylin and eosin (H&E) staining. RESULTS: Eight weeks of aerobic exercise significantly mitigated diabetes-induced cardiac atrophy, increasing the absolute heart weight by 48.9% (0.911 ± 0.048 g vs. 0.612 ± 0.057 g, p < 0.001) and normalizing the relative heart weight. Exercise led to a 41.4% increase in total cardiac volume, a 103% increase in cardiac muscle volume, and improvements in myocyte dimensions in diabetic rats. Additionally, exercise reduced pathological remodeling by decreasing connective tissue volume (7.1% reduction) and restoring vascular bed architecture (22.4% reduction), with significant exercise × diabetes interactions (p < 0.01). CONCLUSION: This study provides robust stereological evidence that aerobic exercise protects against diabetic cardiomyopathy by reversing cardiac atrophy, increasing muscle volume, reducing pathological fibrosis, and normalizing vascular architecture. These findings highlight aerobic exercise as a promising nonpharmacological intervention for preventing diabetes-induced cardiac structural deterioration.