Evaluation of cardiac histology and cell death markers during the progression of diabetes in a streptozotocin-induced diabetes rat modelOA

The simultaneous characterization of histological alterations and distinct celldeath pathways associated with diabetic cardiomyopathy(DCM)has not beencomprehensively explored and may differ depending on the experimental model.Weevaluated cardiac histological changes and markers of apoptosis,cell death associatedwith mitochondrial permeability transition pore(mPTP)opening(necrosis),andautophagy in early and advanced stages of streptozotocin(STZ)-induced diabetesin rats receiving insulin daily to prevent mortality while maintaining hyperglycemia.Adult male Sprague–Dawley rats(n=4–5)were randomly assigned to receive STZ(diabetic group)or saline(mock)and followed up for 4 or 12 weeks.Hearts wereprocessed for histological examination and immunohistochemical detection of activecaspase-3,beclin-1,and cyclophilin D.STZ significantly increased glycemia at bothtime points,whereas body weight reduction was observed only at 12 weeks.Noevidence of cardiac hypertrophy,fibrosis,or structural injury was detected in diabeticrats at either stage.Expression of caspase-3,beclin-1,and cyclophilin D decreased at12 weeks compared with 4 weeks,regardless of treatment;however,cyclophilin D waselevated in diabetic hearts at 4 weeks.These results suggest an early susceptibilityto mPTP opening under persistent hyperglycemia,despite the absence of overthistological damage.They also underscore the critical importance of insulin dosingand study duration when interpreting data from STZ-based models.Further studiesare warranted to determine how even minimal insulin administration may shape thetemporal dynamics of cell death during the progression of DCM.