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

作　　者：赵昱 吴军[1] 安扬 常青[1] ZHAO Yu;WU Jun;AN Yang;CHANG Qing(Department of Anesthesiology,Heilongjiang Provincial Hospital,Harbin Heilongjiang 150036,China)

机构地区：[1]黑龙江省医院麻醉科,黑龙江哈尔滨150036

出　　处：《蚌埠医学院学报》2021年第5期570-573,578,共5页Journal of Bengbu Medical College

基　　金：黑龙江省卫生健康委科研课题(2019-136)。

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15μg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。Objective:To investigate the role of spinal colony-stimulating factor 1(CSF1)in morphine tolerance to analgesia.Methods:Male 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 15μg 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.Results:Intrathecal 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).Conclusions:CSF1 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.

关 键 词：吗啡 镇痛耐受 集落刺激因子1 小胶质细胞 

分 类 号：R971.1[医药卫生—药品]