Cornin protects astrocytes against autophagy induced by cerebral ischemia-reperfusion via PI3K/Akt/mTOR pathway

OBJECTIVE The purpose of this study was to investigate the effect of cornin against astrocytes autophagy induced by cerebral ischemia-reperfusion and its mechanism. METHODS In vitro, U87 cells were used to establish oxygen glucose deprivation/reperfusion（OGD/R） as a cerebral ischemia model. In vivo, a SpragueDawley（SD） rat middle cerebral artery occlusion（MCAO） model was used to evaluated the effects of cornin against autophagy in astrocytes. RESULTS The results demonstrated that cornin was able to increase the ratio of apoptosis regulator Bcl-2/Bax and decrease the level of cleaved-caspase-3 protein. Similarly, cornin reduce the rate of apoptotic cells by flow cytometry. In addition, cornin(100 nmol·L;) decreased the expression of microtubule-associated proteins 1A/1B light chain 3 B（LC3-Ⅱ） and Beclin-1 protein, increased the level of p62,and upregulated phosphorylated protein kinase m TOR（m TOR）, phosphorylated（p） RAC α serine/threonine protein kinase（Akt） in OGD treated U87 cells. However,following PI3 K inhibitor LY294002 and m TOR si RNA reversed this result. Cornin(10 mg · kg;) significantly reduced the cerebral infarction volume and the leakage rate of blood-brain barrier（BBB）. The expression of autophagy proteins（LC3-Ⅱ, Beclin-1, P62） and apoptosis-associated proteins（Bcl-2/Bax, cleaved caspase-3） in brain tissue showed the similar results as in cells. Similarly, PI3 K inhibitor LY294002 was able to reversed the protective effect of cornin and upregulate autophagy-associated proteins. In addition, immunohistochemistry staining was applied for Neu N, GFAP, LC3 B and Beclin-1, and cornin could alleviated pathological injury 24 h after ischemiareperfusion. CONCLUSION These results indicated that cornin against astrocytes autophagy induced by cerebral ischemia-reperfusion through PI3 K/Akt/m TOR signaling pathway.