脊髓CSF-1诱发小胶质细胞活化在长春新碱诱导神经病理性疼痛大鼠中的作用  

The role of CSF-1-induced microglia activation in neuropathic pain induced by vincristine in rats

作　　者：付宝军[1] 姜静静[1] 黄玉琼 林宗航[1] 李恒[1] Fu Baojun;Jiang Jingjing;Huang Yuqiong;Lin Zonghang;Li Heng(Department of Anesthesiology,the Sixth Affiliated Hospital of Guangzhou Medical University,Qingyuan People’s Hospital,Qingyuan 511518,China)

机构地区：[1]广州医科大学附属第六医院清远市人民医院麻醉科,清远511518

出　　处：《新医学》2020年第7期522-527,共6页Journal of New Medicine

基　　金：广东省医学科研基金(A2019050);清远市科技计划项目(2018B066)。

摘　　要：目的探讨脊髓集落刺激因子1(CSF-1)诱发小胶质细胞活化在长春新碱诱导神经病理性疼痛大鼠中的作用。方法采用随机数表法将30只健康雄性SD大鼠分为3组(每组10只):对照组(Control组)、化学治疗痛组(CINP组)、化学治疗痛+CSF-1中和抗体组(CINP+anti组)。化学治疗药物诱导的神经病理性疼痛动物模型采用隔日腹腔注射长春新碱125μg/kg(共计4次)的方法建立,CINP+anti组在CINP组的给药基础上加予CSF-1中和抗体。于首次注射长春新碱前及注射后1、3、5、7 d采用机械缩足反射阈值(MWT)和热缩足反射潜伏期(TWL)评价大鼠机械痛敏和热痛敏;采用蛋白免疫印迹法检测脊髓CSF-1以及脊髓小胶质细胞标志物离子化钙结合适配分子1(Iba1)的表达情况;采用逆转录PCR法检测脊髓CSF-1 mRNA和Iba1mRNA的表达水平。结果与Control组比较,CINP组大鼠在首次注射长春新碱后3、5、7 d的MWT和TWL更低(P均<0.01);与CINP组比较,CINP+anti组首次注射长春新碱后5、7 d的MWT和TWL更高(P均<0.01)。与Control组比较,CINP组脊髓CSF-1、Iba1表达上调(P均<0.01);与CINP组比较,CINP+anti组CSF-1、Iba1表达下调(P均<0.05)。与Control组比较,CINP组脊髓Iba1 mRNA表达上调(P <0.01);与CINP组比较,CINP+anti组脊髓Iba1 mRNA表达下调(P <0.01)。结论长春新碱诱导神经病理性疼痛,其机制可能与大鼠脊髓CSF-1活化脊髓小胶质细胞有关。Objective To investigate the role of spinal colony-stimulating factor 1(CSF-1)-induced microglia activation in rat models with neuropathic pain induced by vincristine.Methods Thirty healthy male SD rats were divided into 3 groups by random number table method(10 rats in each group):control group(control group),chemotherapy-induced neuropathic pain group(CINP group) and chemotherapyinduced neuropathic pain+CSF-1 neutralizing antibody group(CINP+anti group).The CINP rat models were established by intraperitoneal administration of vincristine 125μg/kg on alternate days for 4 times.In the CINP+anti group,CSF-1 neutralizing antibody was supplemented.Mechanical allodynia and heat hyperalgesia were evaluated by mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) before and1-,3-,5-and 7-d after initial administration of vincristine,respectively.The expression levels of CSF-1 and ionized calcium-binding adapter molecule 1(Ibal) proteins were detected by Western blot.The expression levels of CSF-1 and Ibal mRNA were measured by RT-PCR.Results Compared with the control group,the MWT and TWL at 3-,5-and 7-d after vincristine administration were significantly decreased in the CINP group(both P<0.01).The MWT and TWL at 5-and 7-d after vincristine administration in the CINP+anti group were significantly higher than those in the CINP group(both P <0.01).Compared with the control group,the expression levels of CSF-1 and Ibal in the spinal cord were significantly up-regulated in the CINP group(both P <0.01).Compared with the CINP group,the expression levels of CSF-1 and Ibal in the spinal cord were significantly down-regulated in the CINP+anti group(both P<0.05).Compared with the control group,the expression of Ibal mRNA was significantly up-regulated in the CINP group(P <0.01).Compared with the CINP group,the expression of Ibal mRNA was remarkably down-regulated in the CINP+anti group(P<0.01).Conclusion The mechanism of neuropathic pain induced by vincristine may be related to the activation of spinal microg

关 键 词：长春新碱 神经病理性疼痛 小胶质细胞 集落刺激因子1 

分 类 号：R741.041[医药卫生—神经病学与精神病学]