前扣带回皮层中趋化因子CX3CL1对于大鼠慢性病理性疼痛的影响  

Effects of chemokine on chronic neuropathic pain in anterior cingulate cortex

作　　者：支亦博 章洁[2] 郭伟兵[1,2] 陈春龙[2] 李文君[1,2] 刘清珍[2] 刘健[2] 李伟彦[2] ZHI Yi-bo ZHANG Jie GUO Wei-bing CHEN Chun-long LI Wen-jun LIU Qing-zhen LIU Jian LI Wei-yan(Nanjing Clinical College of Southern Medical University Dept of Anesthesiology,Jinling Hospital, Nanjing 210002,China)

机构地区：[1]南方医科大学南京临床医学院 [2]南京军区总医院麻醉科,江苏南京210002

出　　处：《中国药理学通报》2017年第5期622-626,共5页Chinese Pharmacological Bulletin

基　　金：江苏省自然科学基金资助项目(No BK20131328)

摘　　要：目的观察大鼠在慢性疼痛时,前扣带回皮层(anterior cingulate cortex,ACC)中趋化因子CX3CL1的表达对于胶质细胞活化的影响。方法本实验采用大鼠左侧眶下神经结扎模型(unilateral infraorbital nerve,CCI-ION)。80只♂SD大鼠随机分为4组(n=20),分别为假手术组、疼痛组、PBS治疗对照组、CX3CL1中和抗体治疗组。假手术组仅暴露大鼠左侧眶下神经,不予结扎;疼痛组暴露大鼠左侧眶下神经并结扎。这2组分别于1、3、5、7、14 d早晨9∶00进行行为学测试,并且于行为学测试完成之后处死大鼠,取其前扣带回皮层,分别比较趋化因子CX3CL1和CD11b(小胶质细胞标记物)的表达水平。PBS治疗对照组是在眶下神经结扎术后CX3CL1表达水平最高的当天10∶00进行大鼠前扣带回皮层给药,给予PBS溶液。CX3CL1中和抗体治疗组与PBS治疗对照组同一天、同时间于大鼠前扣带回皮层给予CX3CL1中和抗体。两组于给药后6 h进行行为学测试,并于行为学测试完毕后处死大鼠,取前扣带回皮层组织,Western blot分别检测其中CD11b、CX3CL1、白细胞介素1β(IL-1β)的蛋白表达水平。结果各组大鼠术前行为学测试差异无统计学意义(P>0.05);假手术组、疼痛组术后两组相同时间行为学测试发现,疼痛组大鼠左侧V2区痛阈明显下降,差异有统计学意义(P<0.05);两组给药组给药后行为学测试发现给予CX3CL1中和抗体后,大鼠痛阈有明显提高,差异有统计学意义(P<0.05)。结论前扣带回皮层可能通过胶质细胞和趋化因子参与对慢性神经痛的调节。Aim To investigate the effects of chemokine in the anterior cingulate cortex（ACC）of rats on the chronic neuropathic pain.Methods A model of trigeminal neuropathic pain was made by chronic constriction injury to the unilateral infraorbital nerve（CCI-ION）.Eighty male Sprague-Dawley rats were randomly assigned into 4 groups（n=20）： the sham group, the control group, the PBS treatment group and the anti-CX3CL1 treatment group.The unilateral infraorbital nerve was just exposed in the sham group; in the control group, the unilateral infraorbital nerve was exposed and ligated.The behavioral test was measured at 9：00 am on day 1, 3,5, 7, 14 after surgery separately.These rats were executed after behavioral tests, then tissues of ACC were removed to compare the protein expression levels of CX3CL1 and CD11b in two groups.The PBS solution and the CX3CL1 neutralizing antibody were injected into the ACC separately at 10：00 am on the day with the highest level of CX3CL1 protein expression in the PBS treatment group and the anti-CX3CL1 treatment group.The behavioral test was measured 6 h later after the injection, and the tissue of ACC was removed to measure the protein expression levels of CX3CL1, CD11b and IL-1β of the two groups.Results At baseline, there was no significant difference in the feeling threshold among the four groups（P〈0.05）.Compared with the sham group, there was a significant reductionin the feeling threshold in the ipsilateral ION territory from 3 d to 14 d after CCI-ION in the control group（P〈0.05）.Rats given antibody in the anti-CX3CL1 treatment group showed an evident increase of the feeling threshold compared with the PBS group（P〈0.05）.Conclusion The ACC may take part in the chronic neuropathic pain via associating with the activated microglial cell and high-level of CX3CL1 expression.

关 键 词：慢行病理性疼痛 眶下神经结扎 前扣带回皮层 小胶质细胞 趋化因子CX3CL1 CD11B 

分 类 号：R-332[医药卫生] R322.81