Roles of extra-cellular signal-regulated protein kinase 5 signaling pathway in the development of spinal cord injury  

作　　者：Chen-Jun Liu Hai-Ying Liu Zhen-Qi Zhu Yuan-Yuan Zhang Kai-Feng Wang Wei-Wei Xia 

机构地区：[1]Department of Spinal Surgery,Peking University People’s Hospital,Beijing 100044,China [2]Department of Pathology,Peking University People’s Hospital,Beijing 100044,China.

出　　处：《Chinese Medical Journal》2019年第21期2601-2611,共11页中华医学杂志（英文版）

摘　　要：Background:In consideration of characteristics and functions,extra-cellular signal-regulated protein kinase 5(ERK5)signaling pathway could be a new target for spinal cord injury(SCI)treatment.Our study aimed to evaluate the roles of ERK5 signaling pathway in secondary damage of SCI.Methods:We randomly divided 70 healthy Wistar rats into five groups:ten in the blank group,15 in the sham surgery+BIX02188(sham+B)group,15 in the sham surgery+dimethyl sulfoxide(DMSO;sham+D)group,15 in the SCI+BIX02188(SCI+B)group,and 15 in the SCI+DMSO(SCI+D)group.BIX02188 is a specific inhibitor of the ERK5 signaling pathway.SCI was induced by the application of vascular clips(with the force of 30 g)to the dura on T10 level,while rats in the sham surgery group underwent only T9-T11 laminectomy.BIX02188 or DMSO was intra-thecally injected at 1,6,and 12 h after surgery or SCI.Spinal cord samples were taken for testing at 24 h after surgery or SCI.Results:Expression of phosphorylated-ERK5(p-ERK5)significantly increased after SCI.Application of BIX02188 indeed inhibited ERK5 signaling pathway and reduced the degree of spinal cord tissue injury,neutrophil infiltration and proinflammatory cytokine expression,nuclear factor-kB(NF-kB)activation and apoptosis(measured by TdT-mediated 20-deoxyuridine 50-triphosphate nickend labeling,expression of Fas-ligand,BCL2-associated X[Bax],and B-cell lymphoma-2[Bcl-2]).Double immunofluorescence revealed activation of ERK5 in neurons and microglia after SCI.Conclusion:ERK5 signaling pathway was activated in spinal neurons and microglia,contributing to secondary injury of SCI.Moreover,inhibition of ERK5 signaling pathway could alleviate the degree of SCI,which might be related to its regulation of infiltration of inflammatory cells and release of inflammatory cytokines,expression of NF-kB and cell apoptosis.

关 键 词：EXTRACELLULAR SIGNAL-REGULATED PROTEIN KINASE 5 MITOGEN activated PROTEIN KINASE Spinal CORD injury Nuclear factor-κB Apoptosis 

分 类 号：R73[医药卫生—肿瘤]