Resveratrol Pathway Activates p53/SLC7A11/GPX4 Signaling Pathway to Inhibit Ferroptosis and Improve Cerebral Ischemia-reperfusion Injury
Objective To investigate the inhibitory effect of resveratrol on iron death after cerebral ischemia reperfusion and its mechanism.Methods 63 male sprague-dawley rats,weighing 250～280 g,were randomly divided into sham-operated group,MCAO/R group and resveratrol group.The rat disease model was established by using thread-plug method.The dosage of the treated group was 30mg/kg.Zea-longa score was used to evaluate the neurological function of rats 28 days after administration.The brain tis-sues of rats were collected at 24 h after administration.The brain edema was evaluated by weighing method.The levels of Glutathione peroxidase 4(GPX4)and long chain lipoyl coenzyme A synthetase 4(ACSL4)were detected by immunofluorescence staining.The levels of Fe2+,glutathione peroxidase(GSH),superoxide dismutase(SOD)and malonaldehyde(MDA)in the brain issues of each group were detected by the kit.The protein expressions of p53,SLC7A11 and GPX4 in different groups of rat brain were detected by Western Blot.Results Compared with the injured group,the Zea-longa score,the water content,Fe2+and MDA in the brain,and the expression of GSH and SOD in the resveratrol-treated group were significantly decreased,and the results of immunofluorescence staining showed that the content of GSH and SOD in the brain were significantly increased in the resveratrol-treated group,the expres-sion of GPX4 was increased and the expression of ACSL4 was decreased.The results of WB pathway showed that the expression of P53 was decreased and the expression of SLC7A11 was increased in resveratrol treated group.Conclusion Resveratrol inhibits iron death in MCAO/R rats by regulating the p53/SLC7A11/GPX4 signaling pathway,thereby promoting the recovery of neural function after is-chemia/reperfusion.
NETL
NSTL
万方数据
