藁本内酯对慢性神经病理性疼痛模型小鼠的镇痛作用研究  

Analgesic effect of ligustilide on chronic neuropathic pain mouse model

作　　者：李洁佳 王丽云 张灏 尤文慧 朱清 LI Jiejia;WANG Liyun;ZHANG Hao;YOU Wenhui;ZHU Qing(Center for Translational Research in Neuroscience,the Second Affiliated Hospital of Nantong University,Jiangsu 226014;School of Pharmacy,Nantong University)

机构地区：[1]南通大学第二附属医院神经科学转化研究中心,江苏226014 [2]南通大学药学院

出　　处：《南通大学学报（医学版）》2024年第5期403-410,共8页Journal of Nantong University(Medical sciences)

基　　金：国家自然科学基金面上项目(81971243);南通市卫生健康委科研课题指令性立项课题(MS2022013);南通市第一人民医院省部级以上高层次科技项目培育基金项目(YPYJJYB009)。

摘　　要：目的:观察藁本内酯(ligustilide,LIG)对神经病理性疼痛(neuropathic pain,NP)模型小鼠疼痛的干预作用以及初步机制探索。方法:建立经典的坐骨神经保留性神经损伤(spared nerve injury,SNI)和慢性压迫性损伤(chronic constriction injury,CCI)诱导的小鼠NP模型,观察LIG单次给药(20、40、80 mg/kg,腹腔注射)以及反复多次给药(40、80 mg/kg,腹腔注射,1次/d,连续7 d)对SNI以及CCI诱导的机械性触诱发痛的影响;在LIG反复多次给药处理(40、80 mg/kg,腹腔注射,1次/d,连续7 d)末次给药的当天行SNI和CCI手术,观察LIG处理对NP的预防作用;在LIG 80 mg/kg反复给药条件下,于SNI术后第5天,ELISA法测定脊髓L4~5节段中促炎因子TNF-α、IL-1β和IL-6的含量;免疫荧光观察小胶质细胞标志物离子钙结合衔接分子1(ionized calcium binding adaptor molecule 1,IBA-1)的阳性细胞数以分析小胶质细胞激活的情况。结果:成功建立SNI和CCI诱导的小鼠NP模型,LIG单次给药与重复多次给药均能显著缓解SNI和CCI诱导的NP症状,作用至少能维持7 d,无耐受性产生倾向。在有效剂量下,LIG并不干扰动物的运动功能,说明其镇痛作用具有特异性。术前LIG反复多次给药,能预防SNI与CCI诱导的早期机械性触诱发痛,但维持时间有限(1~2 d)。LIG反复给药处理能降低SNI模型中促炎症因子TNF-α、IL-1β和IL-6的含量,抑制SNI诱导的小胶质细胞激活。结论:LIG对NP症状具有改善作用,不产生耐受性,术前反复给药对NP有一定的预防作用。LIG抗NP机制可能与其抑制神经炎症及胶质细胞的激活有关。Objective:To investigate the analgesic effect of ligustilide(LIG)on neuropathic pain(NP)mouse model and its possible mechanism.Methods:The mouse models of NP induced by classic spared nerve injury(SNI)and chronic constriction injury(CCI)of the sciatic nerve were established.The effects of a single administration of LIG(20,40,80 mg/kg,intraperitoneal injection)and repeated administration of LIG(40,80 mg/kg,intraperitoneal injection,once per day,for 7 consecutive days)on mechanical allodynia induced by SNI and CCI were investigated.SNI and CCI were performed on the day of the last administration of LIG(40,80 mg/kg,intraperitoneal injection,once a day for 7 consecutive days),and the preventive effect of LIG treatment on NP was observed.Under the condition of repeated administration of LIG 80 mg/kg,the contents of pro-inflammatory factors such as TNF-α,IL-1β,and IL-6 in the L4-5 spinal cord segment were detected by ELISA on the 5th day after SNI surgery.Immunofluorescence assay was used to observe the number of positive cells for the microglia marker ionized calcium binding adapter molecule 1(IBA-1)to analyze the activation status of microglia.Results:SNI-and CCI-induced NP mouse models were successfully established.Both single administration of LIG and repeated administration of LIG could significantly alleviate SNI-and CCI-induced NP symptoms,and this effect could be maintained for at least 7 days,with no tendency to develop drug tolerance.With an effective dose,LIG did not interfere with the motor function of animals,indicating that its analgesic effect was specific.Repeated administration of LIG before surgery could prevent early mechanical allodynia induced by SNI and CCI,but its maintenance time was limited to 1-2 days.Repeated administration of LIG can decrease the contents of TNF-α,IL-1βand IL-6 in SNI models,and inhibit the SNI-induced activation of microglia.Conclusion:LIG can exert a ameliorative effect on NP symptoms and does not develop tolerance,and repeated administration of LIG before surgery can

关 键 词：神经病理性疼痛 藁本内酯 神经胶质细胞激活 保留性神经损伤 慢性压迫性损伤 小鼠 

分 类 号：R741[医药卫生—神经病学与精神病学]