首页|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

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

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

Mongolian medicine Naru-3maintenance stage of neuropathic painactivation of astrocytesMMP2/IL-1β signaling pathway

宗瑛、曹人郦、李元滨、侯吴琼、李森森、许丽婷、周方婷、黄丰、林娜、苏晓慧、王震、顾艳丽、熊慧、王超、孙赟

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云南中医药大学 中药学院,云南 昆明 650500

中国中医科学院 中药研究所,北京 100700

内蒙古医科大学,内蒙古 呼和浩特 010110

北京中医药大学 东直门医院,北京 100700

中国中医科学院 中医基础理论研究所,北京 100700

中南民族大学 药学院,湖北 武汉 430074

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蒙古族药那如-3 神经病理性疼痛"维持期" 星形胶质细胞活化 MMP2/IL-1β信号通路

国家自然科学基金面上项目国家自然科学基金面上项目国家自然科学基金面上项目国家重点研发计划中国民族医药学会科研项目中国民族医药学会科研项目中国民族医药学会科研项目

8167369582174084818733222022YFC35022022022M2123-0703042022M2122-0703032021Z1214-080302

2024

10.19540/j.cnki.cjcmm.20240204.401

中国中药杂志
中国药学会

中国中药杂志

CSTPCD北大核心
影响因子：1.718
ISSN：1001-5302
年,卷(期)：2024.49(11)