Effects of lncRNA NEAT1 silencing on microglial polarization via IL-10/STAT3 signaling pathway on cerebral ischemia reperfusion injury in rats / 中风与神经疾病杂志

ABSTRACT

@#Objective To investigate the effect of long noncoding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) silencing on cerebral ischemia reperfusion injury (CIRI) in rats by regulating microglia polarization through interleukin (IL)-10/signal transducer and activator of transcription 3 (STAT3) signaling pathway.Methods SD rats were randomly divided into sham operation group (Sham group),CIRI group,CIRI+si-NC group,CIRI+si-NEAT1 group,each group of 24 rats.Except for the Sham group,the rats in the other groups were used to construct the CIRI model by thread occlusion method.After modeling,rats in each group were given corresponding treatments for 7 days.Neurological deficits of rats were scored; brain histopathological changes were observed; the percentage of cerebral infarction volume,the number of M1 and M2 polarization marker positive (Iba1+CD86+,Iba1+CD206+) cells in the positive cells of ionic calcic junction protein molecule 1 (Iba1+),IL-1β,tumor necrosis factor-α (TNF-α),IL-4,IL-10,lncRNA NEAT1,inducible nitric oxide synthase (iNOS),arginase-1 (Arg-1),IL-10 mRNA,IL-10,STAT3,phosphorylated STAT3 (p-STAT3) protein levels in rat brain tissue were detected.Results Compared with Sham group,the CIRI group showed severe pathological damage of brain tissue in rats,neurological deficit score,percentage of cerebral infarction volume,number of Iba1+CD86+,Iba1+CD206+ positive cells,CD86/CD206 ratio,IL-1β,TNF-α,IL-4,IL-10 levels,lncRNA NEAT1,iNOS,Arg-1,IL-10 mRNA levels,IL-10 and p-STAT3/STAT3 protein levels in brain tissue were significantly increased (P<0.05);compared with CIRI group and CIRI+si-NC group,CIRI+si-NEAT1 group had less pathological damage of brain tissue in rats,neurological deficit score,percentage of cerebral infarction volume,number of Iba1+CD86+ positive cells,CD86/CD206 ratio,IL-1β and TNF-α levels,lncRNA NEAT1,iNOS mRNA levels in brain tissue were significantly decreased (P<0.05),the number of Iba1+CD206+cells,IL-4,IL-10 levels,Arg-1,IL-10 mRNA,IL-10 and p-STAT3/STAT3 protein levels were significantly increased (P<0.05). Conclusion Silencing lncRNA NEAT1 may regulate microglial polarization by activating IL-10/STAT3 signaling pathway,thereby ameliorating brain tissue injury in CIRI rats.