赵昱, 吴军, 安扬, 常青. 脊髓集落刺激因子1在大鼠吗啡镇痛耐受中的作用[J]. 蚌埠医学院学报, 2021, 46(5): 570-573, 578. DOI: 10.13898/j.cnki.issn.1000-2200.2021.05.003
    引用本文: 赵昱, 吴军, 安扬, 常青. 脊髓集落刺激因子1在大鼠吗啡镇痛耐受中的作用[J]. 蚌埠医学院学报, 2021, 46(5): 570-573, 578. DOI: 10.13898/j.cnki.issn.1000-2200.2021.05.003
    ZHAO Yu, WU Jun, AN Yang, CHANG Qing. Role of spinal colony-stimulating factor 1 in rats in morphine tolerance to analgesia[J]. Journal of Bengbu Medical College, 2021, 46(5): 570-573, 578. DOI: 10.13898/j.cnki.issn.1000-2200.2021.05.003
    Citation: ZHAO Yu, WU Jun, AN Yang, CHANG Qing. Role of spinal colony-stimulating factor 1 in rats in morphine tolerance to analgesia[J]. Journal of Bengbu Medical College, 2021, 46(5): 570-573, 578. DOI: 10.13898/j.cnki.issn.1000-2200.2021.05.003

    脊髓集落刺激因子1在大鼠吗啡镇痛耐受中的作用

    Role of spinal colony-stimulating factor 1 in rats in morphine tolerance to analgesia

    • 摘要:
      目的观察脊髓集落刺激因子1(CSF1)在大鼠吗啡镇痛耐受过程中的作用。
      方法成功鞘内置管SD大鼠随机分为0.9%氯化钠溶液组(NS组)、吗啡组(MOR组)、CSF1R抑制剂组(PLX3397组)、CSF1R抑制剂+吗啡组(PLX3397+MOR组),各15只。MOR组和PLX3397+MOR组连续7 d鞘内注射吗啡15 μg建立吗啡耐受动物模型,PLX3397+MOR组同时灌胃给予CSF1R抑制剂PLX3397(290 mg/kg);NS组鞘内注射及灌胃给予0.9%氯化钠溶液,PLX3397组鞘内注射0.9%氯化钠溶液,灌胃给予CSF1R抑制剂PLX3397。采用50 ℃热水甩尾潜伏期法和机械反射阈值法观察CSF1在吗啡的镇痛耐受中作用;应用免疫组织荧光染色法检测脊髓背角小胶质细胞激活标志物IBA1表达变化;Western blotting法检测吗啡对腰段脊髓CSF1表达的影响。
      结果连续7 d鞘内注射吗啡,MOR组大鼠最大镇痛效应百分率(percent of maximal possible potential effect,%MPE)进行性降低(P < 0.05);而与MOR组比较,PLX3397+MOR组大鼠注射吗啡3、5、7 d时%MPE均增加(P < 0.05);PLX3397组与NS组各时点%MPE差异均无统计学意义(P>0.05)。注射吗啡7 d后,MOR组小胶质细胞标志物IBA-1在大鼠腰段脊髓背角表达较NS组增加(P < 0.05),MOR+PLX3397组大鼠IBA-1表达较MOR组减少(P < 0.05);MOR组和MOR+PLX3397组大鼠腰段脊髓CSF1表达均较NS组增加(P < 0.05),2组CSF1表达差异无统计学意义(P>0.05)。
      结论脊髓CSF1参与吗啡耐受形成,抑制脊髓CSF1表达可能为临床治疗吗啡镇痛耐受提供一种新的作用靶点。

       

      Abstract:
      ObjectiveTo investigate the role of spinal colony-stimulating factor 1(CSF1) in morphine tolerance to analgesia.
      MethodsMale Sprague-Dawley rats with successful intrathecal catheter were randomly divided into four groups(n=15): 0.9% sodium chloride solution group(NS), morphine group(MOR), CSF1R inhibitor PLX3397 group(PLX3397) and morphine plus PLX3397 group(MOR+ PLX3397).A morphine tolerance model of rats was induced by intrathecal injection of 15 μg morphine once daily for 7 consecutive days in MOR and MOR+PLX3397 group.PLX3397 was administered intragastrically in PLX3397 and MOR+PLX3397 group, 0.9% sodium chloride solution was administered intrathecally in NS and PLX3397 group.The role of CSF1 on morphine antinociceptive tolerance was explored by %MPETFL and %MPEMWT.Immunohistochemistry assay was applied to detect the expression of IBA-1.Western blotting was used to evaluate the change of spinal CSF1 expression.
      ResultsIntrathecal injection of morphine for 7 days, %MPE in MOR group showed progressive decrease, while %MPE in MOR+PLX3397 group were significantly increased as compared with MOR group on day 3, 5, 7 after chronic morphine(P < 0.05);There was no significant difference in %MPE between PLX3397 and NS group(P>0.05).on day 7 after chronic morphine, the expression of IBA-1 in MOR group was significantly up-regulated as compared with NS group(P < 0.05), while the expression of IBA-1 in MOR+PLX3397 group was significantly down-regulated as compared with MOR group(P < 0.05);the expression of CSF1 in MOR and MOR+PLX3397 group was significantly up-regulated as compared with NS group(P < 0.05).
      ConclusionsCSF1 in the spinal cord can be involved in the development of tolerance to morphine-induced analgesia.Inhibition of CSF1 may provide a new therapeutic target for morphine tolerance to analgesia.

       

    /

    返回文章
    返回