Mechanism of analgesic effect of electroacupuncture on rats with cervical spondylosis radiculopathy based on activation of astrocytes and HMGB1/TLR4/MyD88 signaling pathway
Objective To observe effects of electroacupuncture(EA)on the activation of astrocytes and high mobility group protein B1(HMGB1)/Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway,as well as related cytokines in rats with cervical spondylosis radiculopathy(CSR),so as to explore the analgesic mechanism of EA in treating CSR.Methods Twenty-four male SD rats were randomly divided into blank,sham surgery,model,and EA groups,with 6 rats in each group.CSR rat model was established by using cervical spinal cord canal puncture method.On the 7th day after successful modeling,EA was applied to rats in the EA group at bilateral"Hegu"(LI4)and"Taichong"(LR3)for 20 minutes(1.5 Hz,1 mA),once daily for 7 consecutive days.Before and after intervention,gait impairment scores and mechanical pain thresholds were assessed.HE staining was used to observe pathological changes in spinal cord tissue.Western blot was used to detect the expression of HMGB1,TLR4,MyD88,and glial fibrillary acidic protein(GFAP)in the spinal cord.ELISA was used to measure the contents of CXC chemokine ligand 1(CXCL1),chemokine ligand 2(CCL2),tumor necrosis factor(TNF)-α,and interleukin(IL)-1β in spinal cord.Immunofluorescence staining was used to observe GFAP protein positive expression in spinal cord tissue.Results There was no significant difference of all indexes between the blank group and the sham surgery group.Compared with the sham surgery group,mechanical pain threshold of rats in the model group was decreased(P<0.01),while gait impairment score,the contents of CXCL1,CCL2,TNF-α,IL-1β,protein expressions of HMGB1,TLR4,MyD88 and GFAP,and positive expression of GFAP in spinal cord tissue were increased(P<0.01);HE staining indicated severe overall morphological damage in the spinal cord of rats in the model group,with significant shrinkage of gray matter neurons,reduced number of Nissl bodies,and increased inflammatory cell infiltration.Compared with the model group,mechanical pain threshold in the EA group was increased(P<0.01),while gait impairment score,the contents of CXCL1,CCL2,TNF-α,IL-1β,protein expressions of HMGB1,TLR4,MyD88 and GFAP,and positive expression of GFAP in spinal cord were reduced(P<0.01);HE staining showed more intact neuronal cell bodies,increased number of Nissl bodies,and reduced shrinkage of gray matter neurons,inflammatory cell infiltration,and microvascular dilation in the spinal cord of rats in the EA group.Conclusion EA can effectively alleviate pain in CSR rats,which is possibly by inhibiting astrocyte activation,HMGB1/TLR4/MyD88 signaling pathway,and reducing the release of related inflammatory cytokines,thus alleviating central sensitization in spinal segments.
Cervical spondylosis radiculopathyElectroacupunctureAstrocyteChemokineInflammatory cytokineCentral sensitizationHigh mobility group protein B1/Toll-like receptor 4/myeloid differentiation factor 88 signaling pathway
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维普
