Quercetin activates mitochondrial autophagy via PINK1/parkin pathway to alleviate cerebral ischemia-reperfusion injury in rats

AIM To analyze the regulatory effect of quercetin （QUE） on PTEN-induced putative kinase 1 （PINK1）/parkin mitochondrial autophagy pathway， and to explore the mechanism of quercetin in relieving cerebral ischemia/reperfusion （I/R） injury. METHODS Sixty SD male rats were randomly divided into sham operation group， model group （I/R group）， QUE group，3-methyladenine （3-MA） group and QUE+3-MA group. Administration started in each group 3 days before modeling， once a day， at 30 min after the last administration，except sham group， the other groups used 4-vessel blockage method to establish the whole brain I/R model. On the day after modeling， the neural function was evaluated by neuropathy disability score （NDS）. The volume of cerebral infarction was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. The morphological changes of mitochondria in hippocampus were observed by transmission electron microscopy. The contents of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in hippocampus were measured by ELISA. The activity of superoxide dismutase （SOD） and contents of malondialdehyde （MDA） in hippocampus were detected by xanthine oxidase method， thiobarbituric acid condensation method. Western blot was used to detect the proteinex pression of PINK1， parkin and LC3-II in brain tissue. RESULTS Compared with sham group， the hippocampus of the rats in I/R group and QUE+3-MA group showed swelling of mitochondria， destruction or disappearance of internal crista and other pathological damage，also the volume of cerebral infarction， the contents of IL-6， TNF-α and MDA， the protein expression levels of PINK1， parkin and LC3-II were increased （P<0.05）， while NDS score and activity of SOD were decreased （P<0.05）. Compared with I/R group and QUE+3-MA group， the pathological damage degree of hippocampus in QUE group was reduced， the volume of cerebral infarction， the contents of IL-6， TNF-α and MDA were decreased （P<0.05）， the proteinexpression levels of PINK1， parkin and LC3-II， and NDS score and activity of SOD were increased （P<0.05）.The above indexes in 3-MA group were opposite to QUE group. No significant difference in the above indexes between I/R group and QUE+3-MA group was observed （P>0.05）. CONCLUSION Quercetin activates mitochondrial autophagy and reduces cerebral I/R by regulating the expression of PINK1/parkin pathway proteins.