背根神经节巨噬细胞迁移抑制因子参与调控神经病理性疼痛的机制研究  

Role of migration inhibitory factor in rat model of dorsal root ganglion mediated neuropathic pain

作　　者：龙迎曦[1] 唐轶珣 黄晓玲[1] 潘冰冰[1] 刘永平[1] 魏来[1] 孔高茵[1] Ying-xi Long;Yi-xun Tang;Xiao-ling Huang;Bing-bing Pan;Yong-ping Liu;Lai Wei;Gao-yin Kong(Department of Anesthesiology(Clinical Research Center for Anesthesiology of ERAS in Hunan Province),Hunan Provincial People's Hospital,Changsha,Hunan 410005,China)

机构地区：[1]湖南省人民医院(湖南师范大学附属第一医院)麻醉科(湖南省围术期加速康复麻醉临床医学研究中心),湖南长沙410005

出　　处：《中国现代医学杂志》2018年第33期7-12,共6页China Journal of Modern Medicine

基　　金：湖南省卫生计生委科研基金(No:B2016017)

摘　　要：目的探讨脊髓背根神经节(DRG)巨噬细胞迁移抑制因子(MIF)对神经病理性疼痛的作用及可能的调控机制。方法成年雄性SD大鼠随机分为3组(n=8):假手术组(Sham组)、坐骨神经结扎(CCI)模型对照组(以下简称CCI组)、ISO-1组(CCI+鞘内注射ISO-1)。鞘内置管5 d后予以左侧坐骨神经结扎。CCI组和ISO-1组连续14 d鞘内注射10%DMSO 10μl或含ISO-1 30μg的DMSO 10μl,每天1次。在术前1天,术后第1、3、5、7、10及14天(给药2 h后)测定机械痛阈值;在第7和14天取大鼠DRG,ELISA检测肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)的表达变化,Western blot检测MIF表达变化,并于第14天记录受损坐骨神经传导速度(CV)。结果与Sham组比较,术后CCI组机械痛阈值均降低(P <0.05);与CCI组比较,ISO-1组术后第10和14天机械缩足反射阈值均升高(P <0.05)。与Sham组比较,CCI组第7和14天背根神经节MIF、TNF-α、IL-1β表达上调(P <0.05);与CCI组比较,ISO-1组第7和14天MIF、TNF-α、IL-1β表达下调(P <0.05)。神经电生理的结果显示,与Sham组比较,CCI大鼠坐骨神经的CV降低,差异有统计学意义(P <0.05);ISO-1组与CCI组大鼠坐骨神经的CV比较,差异无统计学意义(P>0.05)。结论鞘内注射MIF拮抗剂ISO-1可以减轻大鼠机械痛敏,下调DRG MIF、TNF-α和IL-1β表达,但不能修复受损坐骨神经。MIF拮抗剂ISO-1可能通过抑制脊髓背根神经节炎症反应,减轻大鼠神经病理性疼痛。Objective To investigate the role of macrophage migration inhibitory factor(MIF)in dorsal root ganglion(DRG)mediated neuropathic pain.Methods Animals in all groups were intrathecally catheterized 5 days before surgery.SD rats were randomized into three groups(n=8):sham group in which rats received all surgical procedure except nerve ligation,CCI group in which rats received CCI and intrathecal injection of 10%DMSO(10μl per day for 2 weeks),and ISO-1 group in which rates received CCI and intrathecal injection of ISO-1(30 ug/ul per day for 2 weeks).Mechanical allodynia of the plantar surface of the left hind-paw was tested on 1st d before surgery,1st d,3rd d,5th d,7th d,10th d,and 14th d after surgery in all rats(2h after intrathecal injection).The expressions of MIF,TNF-αand IL-1βin DRG were examined by western blot or ELISA on the 7th and 14th day after surgery.The Conduction Velocity(CV)of sciatic nerve was tested on the 14th day after surgery.Results Paw mechanical withdrawal threshold(PMWT)in CCI group was significantly lowered compared with sham group(P<0.05),which was abolished by treatment of ISO-1 on 5th d,7th d,10th d,and 14th d after surgery(P<0.05).Westernblot and ELISA showed that the expression of MIF,TNF-α,and IL-1βin CCI group was markedly increased in the ipsilateral DRG on the 7th and 14th day after nerve injury when compared with sham group(P<0.05),which was significantly suppressed by ISO-1 admission(P<0.01).Electrophysiology test showed that CV was decreased greatly in the CCI group compared with that in sham group while no difference was observed between CCI and ISO-1 groups.Conclusions MIF antagonist ISO-1attenuates tactile allodynia without obvious physical recovery of sciatic nerve through attenuating local inflammation,suggesting that blockage of MIF might be a therapeutic strategy for treating neuropathic pain.

关 键 词：神经病理性疼痛/神经痛 巨噬细胞迁移抑制因子 ISO-1 促炎细胞因子 

分 类 号：R614[医药卫生—麻醉学]