Experimental Validation of Diabetic Cardiomyopathy in High-Fat Diet and Streptozotocin-Induced Diabetic Rats Through Mitochondrial Dysfunction, Cardiac Collagen Remodeling and Histopathological Assessment

Abstract

Background

Diabetes mellitus is a major metabolic disorder associated with progressive cardiovascular complications. Diabetic cardiomyopathy (DCM) represents diabetes-associated myocardial structural and functional impairment that develops independently of overt coronary artery disease and other primary cardiac disorders. Mitochondrial dysfunction, excessive oxidative stress, altered myocardial energy metabolism, extracellular matrix remodeling and cardiac fibrosis are recognized contributors to the development and progression of DCM. The present study was designed to establish and validate diabetic cardiomyopathy in rats using a high-fat diet (HFD) combined with streptozotocin (STZ) and to evaluate myocardial injury through mitochondrial functional integrity, cardiac collagen remodeling and histopathological examination.

Methods

Male Wistar rats were randomly allocated into five experimental groups: normal control, diabetic control, and three treatment groups. Experimental diabetes was induced by administration of a high-fat diet followed by streptozotocin administration according to the established experimental protocol. Following confirmation of diabetes, the respective treatment interventions were administered to the treatment groups. At the end of the experimental period, animals were sacrificed under approved experimental conditions and cardiac tissue was collected. Myocardial mitochondrial function/integrity was assessed using mitochondrial assay(s)], while cardiac collagen remodeling was evaluated using collagen marker.  Histopathological examination of cardiac tissue was performed using hematoxylin and eosin staining. Data were expressed as mean ± SEM/SD and analyzed using graph pad prism.

Results

The diabetic control group demonstrated marked metabolic and cardiac alterations compared with the normal control group. Diabetes-associated impairment of myocardial mitochondrial function was observed together with increased cardiac collagen remodeling and pathological histological alterations. The cardiac tissue of diabetic animals showed evidence of structural injury, including: myocyte hypertrophy, degeneration, inflammatory infiltration, interstitial fibrosis, vascular changes, etc.]. Treatment groups demonstrated attenuation of these abnormalities, as reflected by improved mitochondrial functional integrity, reduced collagen-associated cardiac remodeling and improvement in histopathological architecture. The observed changes support the development of a diabetic cardiac phenotype in the HFD-STZ model and indicate a cardioprotective effect of the investigated interventions.

Conclusion

The present study demonstrates that HFD combined with STZ can produce a cardiac phenotype characterized by mitochondrial impairment, extracellular matrix/collagen remodeling and histopathological abnormalities. Assessment of mitochondrial function, cardiac collagen content and myocardial histology provides complementary evidence for experimental validation of diabetic cardiomyopathy. The attenuation of these abnormalities in the treatment groups suggests a protective effect against diabetes-associated myocardial injury.