MicroRNA 381 Favors Repair Of Nerve Injury Through Regulation Of The SDF-1/CXCR4 Signaling Pathway Via LRRC4 In Acute Cerebral Ischemia After Cerebral Lymphatic Blockage

Background/Aims: Acute cerebral ischemia is a manifestation of cerebral vascular insufficiency and has a high mortality.However,the therapy for acute cerebral ischemia is still limited.This study aimed to investigate the effect of micro RNA 381(mi R-381)on the repair of nerve injury in rats with acute cerebral ischemia after cerebral lymphatic blockage(CLB)by targeting leucine-rich repeat C4 protein(LRRC4)through the Stromal cell-derived factor-1/CXC chemokine receptor-4 signaling pathway.Methods: Rat models of CLB and middle cerebral artery occlusion(MCAO)were established,and 56 Wistar rats were divided into sham,MCAO,CLB + MCAO,CLB + MCAO + micro RNA 381 inhibitor,CLB + MCAO +micro RNA 381 mimic,CLB + MCAO + AMD3100 and CLB + MCAO +micro RNA 381 mimic + AMD3100 groups.Modified neurological severity score(m NSS was used to determine nerve injury,TTC staining to measure infarction volume,terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling(TUNEL)staining and flow cytometry to evaluate cell apoptosis,immunofluorescence to measure Brd Upositive cell number,enzyme-linked immunosorbent assay(ELISA)to determine contents of tumor necrosis factor-?(TNF-?),interleukin-1?(IL-1?),interleukin-6(IL-6),interleukin-10(IL-10),nerve growth factor(NGF)and neurite outgrowth inhibitor-A(Nogo-A),Reverse transcription quantitative polymerase chain reaction(RT-q PCR)and Western blotting to evaluate expression of micro RNA381,LRRC4,SDF-1,CXCR4,ERK,Slit2 and vascular endothelial growth factor(VEGF).Results: LRRC4 was a target gene of micro RNA 381.Compared with the results in the CLB + MCAO group,m NSS,infarction volume,apoptosis rate and TNF-?,IL-1?,IL-6 and Nogo-A contents as well as LRRC4 expression in the CLB + MCAO + micro RNA 381 inhibitor and CLB + MCAO + AMD3100 groups were increased(those in the CLB + MCAO + AMD3100 group > those in the CLB + MCAO + micro RNA 381 mimic + AMD3100 group),while Brd U-positive cell number,contents of NGF and IL-10,and expression of SDF-1,CXCR4,p ERK,Slit2 and VEGF in brain tissues were decreased(those in the CLB + MCAO + AMD3100 group < those in the CLB + MCAO +micro RNA 381 mimic + AMD3100 group).The results in the CLB + MCAO +micro RNA 381 mimic group were opposite of those in the CLB + MCAO +micro RNA 381 inhibitor and CLB + MCAO + AMD3100 groups.Conclusion: Taken together,we concluded that up-regulation of micro RNA 381 promoted nerve injury repair in acute cerebral ischemia ratsafter CLB by negatively regulating LRRC4 through activating the SDF-1/CXCR4 signaling pathway.