基础医学与临床 ›› 2015, Vol. 35 ›› Issue (8): 1061-1066.

• 研究论文 • 上一篇    下一篇

依那西普缓解腰椎间盘突出模型大鼠的痛觉过敏并减少趋化因子CCL2和受体的表达

朱翔,戴林,朱铭镝   

  1. 南通大学附属医院
  • 收稿日期:2014-06-20 修回日期:2015-03-28 出版日期:2015-08-05 发布日期:2015-07-15
  • 通讯作者: 朱铭镝 E-mail:mingdizhu@hotmail.com
  • 基金资助:
    南通大学杏林学院科研基金项目;南通市社会事业科技创新与示范项目

Etanercept alleviates lumbar disc herniation-induced hyperalgesia and mRNA expressions of chemokine CCL2/CCR2 in DRG and spinal cord of rats

  • Received:2014-06-20 Revised:2015-03-28 Online:2015-08-05 Published:2015-07-15

摘要: 目的 观察鞘内注射肿瘤坏死因子(TNF-α)抑制剂依那西普(Etanercept)对腰椎间盘突出模型大鼠痛觉过敏的影响及背根神经节(DRG)和脊髓中趋化因子CCL2和其受体CCR2的表达变化。方法 将大鼠随机分为:正常组(Control组);假手术组(Sham组);自身髓核植入组(NP组);NP+Vehicle(Vehicle组);NP+Etanercept(10 mg)(10 mg组);NP+Etanercept(100 mg)(100 mg组)。测定术前1d及术后不同时间点左后爪机械性缩爪阈值(MWT)。实时荧光定量PCR法检测TNF-α、CCL2/CCR2 mRNA表达;免疫组化检测DRG中ED-1和ATF3的表达。结果 1) 与Sham组相比,NP组MWT在术后1d明显降低(P < 0.001),持续21d(P < 0.001)以上; 2)鞘内注射依那西普(100 ?g),在2,3,4 d (P < 0.001)都能缓解NP诱导的机械触痛觉过敏; 3)术前鞘内注射依那西普(100 ?g),抑制了DRG和脊髓中CCL2和CCR2 mRNA的上调。 结论 鞘内注射依那西普能抑制自体髓核移植所致的神经病理性疼痛,其机制可能与抑制CCL2/CCR2的上调有关。

关键词: 腰椎间盘突出症, 脊髓, 背根神经节, TNF-α, CCL2, CCR2

Abstract: Objective: To observe the effects of tumor necrosis factor-? (TNF-?) inhibitor etanercept on hyperalgesia of rats with lumbar disc herniation, as well as on the expression of chemokine CCL2 and its receptor CCR2 in DRG (dorsal root gangalion) and spinal cord. Methods: SD rats were randomly divided into six groups: Normal group (Control), Sham group (Sham), Nucleus pulposus transplantation Group (NP), NP + Vehicle group (Vehicle), NP + Etanercept 10 ?g (Etanercept 10 ?g), NP + Etanercept 100?g(Etanercept100?g).The mechanical withdrawal threshold (MWT) of the left hind paw of rats in different group was measured at 1 d before and different time points after the surgery. The real-time quantitative PCR was used to measure the mRNA expression level of TNF-α, CCL2/CCR2; Immunohistochemical staining was applied to investigate the expression of ED-1 and ATF3 in DRG. Result (1) Compared with Sham group, MWT in NP group was reduced significantly from1 d after the operation (P < 0.001), and lasted for more than 21 d (P < 0.001); (2) Intrathecal injection of etanercept (100 mg) attenuated the NP-induced mechanical allodynia at 2,3,4 d (P < 0.001); (3) Pretreatment of etanercept (100 mg ) inhibited the up-regulation of CCL2 and CCR2 mRNA in both DRG and spinal cord. Conclusion: Intrathecal injection of etanercept inhibits the neuropathic pain caused by the auto transplantation of nucleus pulposus. The mechanisms may be partly due to the inhibition of CCL2/CCR2 upregulation.

Key words: Keywords: Lumber disc herniation, spinal cord, DRG, TNF-α, CCL2, CCR2