蒙古族药那如-3抑制星形胶质细胞活化对神经病理性疼痛“维持期”神经炎症的干预作用

Mongolian medicine Naru-3 reduces neuroinflammation in maintenance stage of neuropathic pain by inhibiting astrocyte activation

神经病理性疼痛(NP)临床治疗棘手,其表型相似但不同病理阶段病机各异,靶向干预NP不同病理阶段核心调控元件成为近年来药物研发新方向并为NP的救治提供了可能。蒙古族药那如-3(NR-3)临床治疗坐骨神经痛、三叉神经痛等全程皆效,但机制不明。该研究在前期“启动期”研究的基础上,建立小鼠脊神经结扎(SNL)模型并采用行为学检测痛敏阈值变化,结合网络分析、Western blot、免疫荧光、ELISA检测、激动剂/拮抗剂等探讨NR-3治疗NP“维持期”的药效机制。结果显示,NR-3可以提高“维持期”SNL小鼠机械痛敏与热痛敏阈值而对正常小鼠基础痛阈无明显影响。实验进一步以背根神经节(DRG)、病变脊髓节段为研究对象发现NR-3对NP“维持期”发挥镇痛作用机制可能与其破坏DRG、脊髓星形胶质细胞的基质金属蛋白酶2(MMP2)/白细胞介素-1β(IL-1β)炎症通路相关。相关研究丰富了NR-3治疗NP“维持期”的生物学内涵,并为其临床合理用药提供了参考。

Neuropathic pain(NP)is difficult to be treated since it has similar phenotypes but different pathogenesis in different pathological stages.Targeted intervention of the core regulatory elements at different pathological stages of NP has become a new direction of drug research and development in recent years and provides the possibility for the treatment of NP.The Mongolian medicine Naru-3(NR-3)is effective in the treatment of sciatica and trigeminal neuralgia,the mechanisms of which remain unknown.On the basis of the previous study of the priming stage,this study established the mouse model of spinal nerve ligation(SNL)and measured the changes of pain thresholds by behavioral tests.The network analysis,Western blot,immunofluorescence assay,ELISA,and agonist/antagonist were employed to decipher the mechanism of NR-3 in the treatment of NP in the maintenance stage.The results showed that NR-3 increased the mechanical and thermal pain thresholds of SNL mice,while it had no significant effect on the basal pain threshold of normal mice.NR-3 may relieve the pain in the maintenance stage of NP by blocking the matrix metalloproteinase 2(MMP2)/interleukin-1β(IL-1β)pathway in the astrocytes of the dorsal root ganglion(DRG)and spinal cord.The findings have enriched the biological connotation of NR-3 in the treatment of the maintenance stage of NP and provide reference for the rational use of this medicine in clinical practice.