CCL3对大鼠糖尿病神经病理性疼痛的影响  

Influence of chemokine CCL3 in spinal cord on diabetic neuropathic pain in rats

作　　者：彭志锋[1] 刘颖[1] 李晨旭[1] Zhi-feng Peng;Ying Liu;Chen-xu Li(Department of Physiology,School of Medicine,Shanxi Datong University,Datong,Shanxi 037009,China)

机构地区：[1]山西大同大学医学院生理教研室,山西大同037009

出　　处：《中国现代医学杂志》2018年第35期6-11,共6页China Journal of Modern Medicine

基　　金：山西省基础研究项目(No:2015021178);山西大同大学博士科研启动经费(No:2014-B-01)

摘　　要：目的探讨脊髓趋化因子配体3(CCL3)在链脲佐菌素(STZ)诱导大鼠糖尿病神经病理性疼痛模型中的作用。方法将SD大鼠随机分成对照组和STZ组。STZ组进一步分为CCL3组、IgG2A组,以及A438079组、PBS组,STZ注射前1 d经鞘内注射CCL3和A438079,1次/d,持续7 d。采用免疫组织化学法检测大鼠脊髓背角(SDH)Iba1的表达,实时荧光定量聚合酶链反应检测CCL3及其受体CCR1、CCR5和P2X7R mRNA表达水平,von Frey细丝法测定大鼠机械痛阈值。结果大鼠腹腔注射STZ后机械刺激痛阈降低(P<0.05)。大鼠SDH小胶质细胞数量增加(P<0.05)。与此同时,STZ组大鼠SDH中CCL3、CCR5 mRNA表达增加(P<0.05)。鞘内注射CCL3中和抗体能减轻STZ诱导的大鼠机械性痛觉过敏(P<0.05)。P2X7R选择性拮抗剂A438079能缓解STZ所致痛觉过敏(P<0.05)。结论大鼠SHD中CCL3和P2X7R有助于STZ诱导的痛觉过敏。Objective To investigate the role of C-C motif chemokine ligand 3(CCL3)in streptozotocin(STZ)-induced diabetic neuropathic pain in rats.Methods Sprague-Dawley rats were randomly divided into a control group and an STZ group.The rats in the STZ group were injected intraperitoneally with STZ and those in the control group were injected with the same amount of normal saline.The STZ group was further divided into CCL3,IgG2A,A438079[selective antagonist of purinoceptor P2X7(P2X7R)]and PBS subgroups;and CCL3,IgG2A,A438079 and PBS were injected intrathecally into the corresponding subgroups once a day from the day before STZ injection for 7 consecutive days.The expression of Iba1 after STZ administration in the spinal dorsal horn(SDH)was detected by immunohistochemistry.The expressions of CCL3,chemokine receptor CCR5 and P2X7R mRNAs were evaluated by qRT-PCR.Mechanical withdrawal threshold was measured after STZ administration by von Frey filament test.Results In the STZ group there was a remarkable decrease in paw withdrawal threshold in response to mechanical stimulation(P<0.05),and a significantly increased number of microglia in the SDH(P<0.05).Meanwhile,STZ-treated rats showed a significant increase in the expressions of CCL3 and CCR5 mRNAs in the SDH(P<0.05).Intrathecal administration of the CCL3-neutralizing antibody attenuated the development of STZ-induced mechanical allodynia(P<0.05).A438079 had preventive effect on STZ-induced allodynia(P<0.05).Conclusions Our findings suggest a contribution of CCL3 and P2X7R in the SDH to STZ-induced allodynia.

关 键 词：糖尿病 疼痛 神经病学表现 疾病模型 动物 链脲佐菌素 趋化因子配体3 

分 类 号：R364[医药卫生—病理学]