Exogenous Adipokine Peptide Resistin Protects Against Focal Cerebral Ischemia/Reperfusion Injury In Mice

Objective: The effect of exogenous adipokine peptide Resistin was observed on the middle cerebral artery occlusion(MCAO).In this study,we detected the changes of infarct size,apoptosis proteins and expression of signal pathways after MCAO,to explore the mechanism of protection by Resistin.Materials and methods: We simulate the cerebral ischemia reperfusion by MCAO.Resistin was injected into the lateral ventricle,and the changes of cerebral ischemia area in mice were detected by TTC staining.Western Blotting was used to detect the expression of PARP-1,Bax,t-Akt and p-Akt 24 hours after cerebral ischemia,and PI3K/Akt inhibitor(wortmannin)was used to reverse the protective effect of Resistin.Foot?fault Test,Foot?fault Test and Rotarod Test were used to detect the improvement of mouse behavior after 14 days.ATP Assay Kit was used to detect the change of tissue ATP level under the intervention of Resistin after MCAO.At the same time,the effects of Resistin on the diet and blood sugar of mice were measured.Results: In study,TTC staining was used to verify the change of the area of cerebral ischemia on the next day after ischemia reperfusion,and it was found that Resistin significantly reduced the ischemic area.We used western blot to detect that Resistin can reduce expression of PARP-1 and Bax and increase the phosphorylation level of Akt after ischemia reperfusion.This effect can be specifically inhibited by P13K/AKT signal pathway inhibitor wortmannin.After cerebral ischemia 45 minutes and reperfusion for 24 hours,the ischemic side of the brain was collected and the content of ATP was detected.It showed that Resistin could significantly increase the level of ATP in the ischemic brain.To determine whether there is a late protection of resistin,we examined neurological function recovery at 14 days after Resistin treatment.In the rotarod test,the time for standing on the rotating rod in I/R group was significantly shorter than sham group.Resistin treatment attenuated this effect.In the grip-traction test,the time to fall from plastic rope in I/R+R group was longer than that in I/R group.In the foot-fault test,the number of foot-faults in I/R+R group was less than that in I/R group.Meanwhile,we found that Resistin did not affect the blood glucose and food intake of mice.Conclusion: The administration of exogenous Resistin in the lateral ventricle has a significant protective effect on cerebral ischemia reperfusion in mice.Resistin can decrease apoptosis by increasing the phosphorylation level of Akt,and can increase the energy supply of tissue after MCAO without influencing food intake and blood sugar.