AMPK/mTOR-mediated therapeutic effect of metformin on myocardial ischaemia reperfusion injury in diabetic rat

BACKGROUND: The autophagy associated signalling pathways such as AMPK/mTOR previously were suggested to play a crucial role in protecting from ischemia-reperfusion injury (IRI). The objective of this study was to evaluate the effect of metformin (DMBG) on autophagy during myocardial IRI with diabetes mellitus (DM). METHODS: The DM rat model was established using streptozocin, and further induced ischemia model via transitory ligation of the left anterior coronary artery and following reperfusion. The model rats were treated with 400 mg/kg/day DMBG for one week. Autophagosomes were investigated using transmission electron microscopy. Autophagy-associated signalling pathways were detected by western blot. RESULTS: The myocardial infarct size was shown to significantly increase in the DM rats exposed to IRI compared to negative control, but decrease in DMBG treated. The mature autophagosomes were elevated in infarction and marginal zones of DM+IRI+DMBG compared to DM+IRI. Furthermore, the increasing protein levels of LC3-II, BECLIN 1, autophagy related 5 (ATG5) and AMP-activated protein kinase suggested activated autophagy-associated intracellular signalling AMPK and mTOR pathways upon DMBG treated. CONCLUSIONS: Taken together, the outcomes demonstrated that DMBG could activate autophagy process to provide a cardio-protective effect against DM induced myocardial IRI.