Resveratrol alleviates cerebral ischemia/reperfusion injury in mice by promoting mitophagy / 中国药理学通报

ABSTRACT

Aim: To investigate the effects of resveratrol (Res) pretreatment on focal cerebral ischemia/reperfusion (I/R) injury and the possible mechanism. Methods: Transient focal cerebral ischemia was introduced into mice by right middle cerebral artery occlusion (MCAO) technique. For Res treatment, C57BL/6J mice were given an intraperitoneal injection with ' Res per day for 5 days. After 24 h of reperfusion, infarct volume, neurological function were assessed. Western blot was used to analyse the expression of silent information regulator 1(SIRT1), mitophagy-relat-ed proteins, and the distribution of cytochrome C (CytC). Flow cytometry assay was introduced to test mitochondrial membrane potential (MMP). A micro-plate reader was used to detect the cellular adenosine triphosphate (ATP) levels. Transmission electron microscopy (TEM) was conducted to observe mitochondrial morphology. Results: Res pretreatment reduced infarct volume and neurological deficit, improved the expression of SIRT1 and mitophagy. Meanwhile, Res attenuated CytC release, recovered MMP, and improved ATP levels. TEM results showed Res could protect the mitochondria from I/R injury-induced destruction. However, as 3-MA was used to inhibit the activation of mitophagy, the protective effects of Res on neurological and mitochondrial function were reversed. Conclusions: Res pretreatment could relieve cerebral I/R injury. The mechanism might be associated with the regulation of mitophagy to maintain mitochondrial structural and functional integrity.