miR-29c-5p Aggravates Ischemic Stroke Reperfusion Injury by Promoting Ferroptosis via Downregulation of LRP6
Objective:To investigate the mechanism of miR-29c-5p in regulating ferroptosis in cerebral ischemia-reperfusion injury.Methods:In this study,male SD rats were subjected to middle cerebral artery occlusion(MCAO)surgery and then reperfused.Neurological function scores and TTC staining were used to assess brain injury and infarct volume.qPCR was used to detect the relative expression level of miR-29c-5p.Western blot was used to detect the expression levels of glutathione peroxidase 4(GPx4)and low-density lip-oprotein receptor-related protein 6(LRP6).The contents of GSH,Fe,and malondialdehyde(MDA)were detected using the corresponding assay kits,and dual luciferase reporter gene assay was used to verify the tar-get gene of miR-29c-5p.Results:With the increase of ischemia-reperfusion time in rats,the relative expres-sion level of miR-29c-5p increased and ferroptosis was aggravated.In addition,agomiR-29c-5p interven-tion also aggravated brain injury and ferroptosis,while antagomiR-29c-5p intervention reversed these effects.Furthermore,combined intervention of agomiR-29c-5p and Fer-1 alleviated brain injury and ferroptosis.The results of dual luciferase reporter gene assay showed that LRP6 is a target gene of miR-29c-5p.Conclusion:In this study,miR-29c-5p promotes ferroptosis and aggravates cerebral ischemia-reperfusion injury in rats by downregulating LRP6.
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