Resveratrol Provides Neuroprotection By Regulating JAK2/STAT3/PI3K/AKT/mTOR Pathway After Stroke In Rats

Objective: To investigate the effect of JAK2/STAT3 and PI3K/AKT/mTOR pathway on resveratrol in cerebral ischemia-reperfusion injury and the relationship between them.Methods: A total of 125 adult male Sprague-Dawley rats(230-270g)were randomly divided into five groups: the sham group(Sham,n = 25),the vehicle middle cerebral artery occlusion(MCAO)group(Veh,n = 25),the resveratrol MCAO group(Res,n = 25),the LY294002(PI3K inhibitor)MCAO group(Res+LY294002,n = 25),and the AG490(JAK2 inhibitor)MCAO group(Res+AG490,n = 25).2% TTC staining was used to measure cerebral infarct volume.neuronal apoptosis was evaluated by TUNEL staining.Proteins and mRNA involved in JAK2/STAT3/PI3K/AKT/mTOR pathway were detected by western blot and RT-qPCR.Results: The results suggested that resveratrol significantly improved neurological function,attenuated cerebral infarct volume,reduced neuronal damage,and markedly decreased neuronal apoptosis;these effects were attenuated by the inhibition of PI3K/AKT with LY294002 and JAK2/STAT3 with AG490.We also found that resveratrol significantly upregulated the expression of p-JAK2,p-STAT3,p-AKT,p-mTOR,and BCL-2 and downregulated expression of cleaved caspase-3 and BAX,which was partially reversed by LY294002 and AG490.Conclusion: These results suggested that resveratrol provides neuroprotective effect against cerebral ischemia-reperfusion injury,which is partially mediated by the activation of JAK2/STAT3 and PI3K/AKT/mTOR.Resveratrol may indirectly upregulate the PI3K/AKT/mTOR pathway by activating JAK2/STAT3.