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

作　　者：宗瑛 曹人郦 李元滨 侯吴琼 李森森 许丽婷 周方婷 黄丰 林娜[2] 苏晓慧[2] 王震[5] 顾艳丽[3] 熊慧[6] 王超[2] 孙赟 ZONG Ying;CAO Ren-li;LI Yuan-bin;HOU Wu-qiong;LI Sen-sen;XU Li-ting;ZHOU Fang-ting;HUANG Feng;LIN Na;SU Xiao-hui;WANG Zhen;GU Yan-li;XIONG Hui;WANG Chao;SUN Yun(College of Traditional Chinese Medicine,Yunnan University of Chinese Medicine,Kunming 650500,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Inner Mongolia Medical University,Hohhot 010110,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;School of Pharmaceutical Sciences,South-Central Minzu University,Wuhan 430074,China)

机构地区：[1]云南中医药大学中药学院,云南昆明650500 [2]中国中医科学院中药研究所,北京100700 [3]内蒙古医科大学,内蒙古呼和浩特010110 [4]北京中医药大学东直门医院,北京100700 [5]中国中医科学院中医基础理论研究所,北京100700 [6]中南民族大学药学院,湖北武汉430074

出　　处：《中国中药杂志》2024年第11期2991-3001,共11页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81673695,82174084,81873322);国家重点研发计划项目(2022YFC3502202);中国民族医药学会科研项目(2022M2123-070304,2022M2122-070303,2021Z1214-080302)。

摘　　要：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.

关 键 词：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 

分 类 号：R29[医药卫生—民族医学]