Diabetic cardiomyopathy (DCM) constitutes a prevalent and severe complication arising from type 2 diabetes, posing a notable risk factor for cardiovascular disease. Patients diagnosed with diabetes are two to three times more susceptible to cardiovascular complications when compared to non-diabetic patients. Adverse cardiovascular events in patients with diabetes are associated with significantly poorer prognoses than those in non-diabetic patients. Trimetazidine (TMZ), recognized for its role in modulating myocardial energy metabolism, exerts regulatory control over free fatty acids (FFA) by inhibiting long-chain 3-KAT within mitochondrial β-oxidation. This inhibition enhances aerobic glucose oxidation, diminishes myocardial fatty acid utilization, sustains adenosine triphosphate (ATP) levels, and optimizes myocardial energy metabolism.

Clinical attention in recent years has focused on trimetazidine, with emerging studies indicating its potential benefits for diabetic cardiomyopathy. However, the precise mechanism remains unclear due to the multifaceted and intricate pathogenesis of diabetic cardiomyopathy, involving factors such as insulin resistance, lipotoxicity, oxidative stress, mitochondrial dysfunction, inflammatory reactions, impaired calcium regulation, endoplasmic reticulum stress, and apoptosis. Based on the conducted research, TMZ is reported to possess various cardiovascular protective mechanisms, with some studies indicating its direct enhancement of myocardial energy metabolism for cell protection.1 Additionally, TMZ exerts an indirect antioxidant effect, impeding myocardial fibrosis, apoptosis, and promoting autophagy.2,3 In particular, severe endoplasmic reticulum stress may induce persistent or excessive protein misfolding, activating the caspase-12-dependent pathway, and thereby playing a distinctive role in the apoptotic process. Therefore, this experiment is conducted to investigate the impact of TMZ on myocardial damage in db/db mice exhibiting diabetic cardiomyopathy and further explore the mechanism.