经颅直流电刺激通过抑制MCP-1/CCR2信号通路减轻膝骨关节炎大鼠疼痛症状OA
Transcranial direct current stimulation alleviates pain in rats with knee osteoarthritis by inhibiting MCP-1/CCR2 signaling pathway
目的 基于单核细胞趋化蛋白1(MCP-1)/趋化因子受体2(CCR2)信号通路,探究经颅直流电刺激(tDCS)减轻膝骨关节炎(KOA)大鼠疼痛的机制.方法 将SD雄性大鼠随机分为假手术组、模型组、tDCS组、tDCS+MCP-1组,每组10只.测定各组大鼠的热缩足潜伏期(TWL)和机械缩足阈值(MWT);采用免疫组织化学检测膝关节组织中疼痛介质神经生长因子(NGF)和背根神经节中离子钙结合衔接分子1(Iba1)蛋白的表达和定位;采用Western blotting检测膝关节组织中白细胞介素(IL)-6、IL-1β的表达,背根神经节中疼痛相关蛋白原肌球蛋白受体激酶A(TrkA)、生长相关蛋白43(GAP43)、降钙素基因相关肽(CGRP)的表达,以及膝关节组织和脊髓中MCP-1、CCR2蛋白的表达.结果 与假手术组比较,模型组大鼠TWL、MWT降低(P<0.05),NGF、IL-6、IL-1β、Iba1、TrkA、GAP43、CGRP、MCP-1、CCR2水平升高(P<0.05);与模型组比较,tDCS组大鼠中上述指标改善(P<0.05);与tDCS组比较,tDCS+MCP-1组大鼠中上述指标被部分逆转(P<0.05).结论 tDCS能够抑制促炎性细胞因子和疼痛相关蛋白,减轻KOA大鼠的疼痛症状,其机制可能与抑制MCP-1/CCR2信号通路有关.
Objective To explore the mechanism by which transcranial direct current stimulation(tDCS)alleviates pain in rats with knee osteoarthritis(KOA)via the monocyte chemoattractant protein 1(MCP-1)/C-C motif chemokine receptor 2(CCR2)signaling pathway.Methods Male SD rats were randomly divided into sham,model,tDCS,and tDCS+MCP-1 groups,with 10 rats in each group.Thermal withdrawal latency(TWL)and mechanical withdrawal threshold(MWT)were measured.The expression and localization of the pain mediator nerve growth factor(NGF)protein in knee joint tissue and ionized calcium-binding adapter molecule 1(Iba1)protein in dorsal root ganglia were detected by immunohistochemistry.The expression of interleukin-6(IL-6)and interleukin-1β(IL-1β)proteins in knee joint tissue,pain-related proteins tropomyosin receptor kinase A(TrkA),growth-associated protein 43(GAP43),and calcitonin gene-related peptide(CGRP)in dorsal root ganglia,and MCP-1 and CCR2 proteins in knee joint tissue and spinal cord was detected by Western blotting.Results Compared with the sham group,TWL and MWT decreased(P<0.05),and the levels of NGF,IL-6,IL-1β,Iba1,TrkA,GAP43,CGRP,MCP-1,and CCR2 increased in the model group(P<0.05).Compared with the model group,these indicators improved in the tDCS group(P<0.05).Compared with the tDCS group,these indicators were partly reversed in the tDCS+MCP-1 group(P<0.05).Conclusion tDCS alleviates pain symptoms in KOA rats by inhibiting pro-inflammatory factors and pain-related proteins,and the mecha-nism may be related to the inhibition of the MCP-1/CCR2 signaling pathway.
郭仁艺;符英杰;林丁;王运成
海南医科大学第一附属医院急救与创伤研究教育部重点实验室,康复科,海口 570102海南医科大学第一附属医院急救与创伤研究教育部重点实验室,康复科,海口 570102海南医科大学第一附属医院急救与创伤研究教育部重点实验室,康复科,海口 570102海南医科大学第一附属医院急救与创伤研究教育部重点实验室,康复科,海口 570102
医药卫生
经颅直流电刺激单核细胞趋化蛋白1趋化因子受体2膝骨关节炎疼痛
transcranial direct current stimulationmonocyte chemoattractant protein 1C-C motif chemokine receptor 2knee osteo-arthritispain
《中国医科大学学报》 2026 (4)
323-328,6
海南省卫生健康行业科研项目(22A200044)
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