The Effects Of MiR-128-3p On Neuroinflammation And Apoptosis After Spinal Cord Ischemia/Reperfusion Injury In Rats Via SP1

Objective: Neuroinflammation and cellular apoptosis caused by spinal cord ischemia/reperfusion(I/R)injury result in neurological dysfunction.MicroRNAs(miRs)have crucial functions in spinal cord I/R injury pathogenesis according to previous evidences.Herein,whether miR-128-3p contributes to spinal cord I/R injury by regulating specificity protein 1(SP1)was assessed.Methods: A rat model of spinal cord I/R injury was established by occluding the aortic arch for 14 minutes.Then,miR-128-3p’s interaction with SP1 was detected by dual-luciferase reporter assays.Next,miR-128-3p mimic and inhibitor,as well as adenovirus-delivered sh RNA specific for SP1 were injected intrathecally for assessing the effects of miR-128-3p and SP1 on rats with spinal cord I/R injury.SP1,Bax and Bcl-2 expression levels in I/R injured spinal cord tissues were evaluated by Western blotting,while IL-1β,TNF-α and IL-6 were quantitated by ELISA.Tarlov scores were obtained to detect hind-limb motor function.Evans blue(EB)dye extravasation was utilized to examine blood-spinal cord barrier(BSCB)permeability.Terminal deoxynucleotidyl transferase mediated d UTP nick end labeling(TUNEL)staining was performed for neuronal apoptosis assessment.Results:MiR-128-3p expression was decreased,while SP1 amounts were increased in rat spinal cord tissue specimens following I/R.SP1 was identified as a miR-128-3p target and downregulated by miR-128-3p.MiR-128-3p overexpression or SP1 silencing alleviated I/R-induced neuroinflammation and cell apoptosis,and improved Tarlov scores,whereas pretreatment with miR-128-3p inhibitor aggravated the above injuries.Inhibition of SP1 reversed the damages induced by miR-128-3p knockdown.Conclusions: Spinal cord ischemia/reperfusion injury induced upregulation of SP1 and downregulation of miR-128-3p.Spinal cord ischemia/reperfusion injury also induced histopathological changes,BSCB permeability increased,and cell apoptosis increased.Overexpression of miR-128-3p protects neurons from neuroinflammation and apoptosis during spinal cord I/R injury partially by downregulating SP1.