CCL3 对大鼠糖尿病神经病理性疼痛的影响

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。

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

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.