持续血浆趋化因子C-X-C基序配体12增加导致疼痛的慢性化  

Continuous increase of chemokine CXCL12 in plasma leads to pain chronicity

作　　者：张辉[1] 麦春林 许雅南 林震嘉 揭英桃 熊媖 唐源 刘先国[2] 谈智[2] 周利君[2] ZHANG Hui;MAI Chun-lin;XU Ya′nan;LIN Zhenjia;JIE Yingtao;XIONG Ying;TANG Yuan;LIU Xianguo;TAN Zhi;ZHOU Lijun(Department of Anesthesiology,Guangdong Second Provincial General Hospital,Guangzhou 510317,China;不详)

机构地区：[1]广东省第二人民医院麻醉科,广州510317 [2]中山大学中山医学院生理教研室及中山大学疼痛研究中心,广州510080

出　　处：《实用医学杂志》2020年第16期2171-2176,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金(编号:81771204);广东省自然科学基金(编号:2019A1515011838,2020A1515010204);广东省第二人民医院引进人才科研启动基金(编号:YY2019-003)。

摘　　要：目的探讨外周神经损伤后血浆趋化因子C-X-C基序配体12(CXCL12)的变化及其在疼痛慢性痛化中的作用。方法采用Western blot和ELISA法检测保留性神经损伤(SNI)经典慢性疼痛模型前后血浆CXCL12时程变化;通过实验观察正常小鼠尾静脉注射外源性CXCL12的痛行为学变化,及静脉注射CXCL12中和抗体对CXCL12与SNI诱导机械痛敏的影响。结果Western blot结果表明SNI 1 d后血浆CXCL12蛋白明显增多,并持续至SNI 9 d;ELISA数据显示血浆CXCL12浓度从对照(35.10±4.11)pg/mL升高到SNI 1d(90.8±8.33)pg/mL(P<0.05)、并持续增加至SNI 21 d(161.20±18.88)pg/mL,P<0.0001。连续9 d静脉注射CXCL12(1.0~5.0 ng/mL,200μL)剂量依赖性引起双侧机械痛觉过敏;而中和血浆CXCL12能缓解静脉注射CXCL12及SNI诱导的双侧机械痛敏。结论血浆CXCL12的持续增加是疼痛慢性化至关重要的因素。Objective To explore the changes of plasma chemokine CXCL12 after peripheral nerve injury and its role in chronic pain.Methods Western blot and ELISA methods were used to detect the temporal profiles of plasma CXCL12 expression before and after spared nerve injury(SNI)in a classical chronic pain model.Then,two positive and negative experiments were performed to observe the changes of pain behavior and investigate the effect of injected neutralizing plasma CXCL12 on CXCL12-and SNI-induced mechanical hyperalgesia.Results By Western blot,CXCL12 were significantly increased in number 1 d after SNI,which remained to grow till 9 d after SNI.By ELISA,the concentration of CXCL12 in the plasma increased from the basal level of(35.10±4.11)pg/ml to(90.8±8.33)pg/mL(SNI Id,P<0.05),progressively to(161.20±18.88)pg/mL 21 d after SNI(_P<0.0001).The consecutive i.v.injection of exogenous CXCL12(1~5μg/p L,200μL)for 9 d dose-dependently induced the bilateral mechanical hyperalgesia.Furthermore,the consecutive i.v.injection of CXCL12-neutralized antibody relieved both CXCL12-induced and SNI-induced bilateral mechanical hypersensitivity.Conclusion The continuous increase of plasma CXCL12 is a critical factor for pain chronicity.

关 键 词：神经病理性疼痛 保留性神经损伤 CXCL12 中和抗体 

分 类 号：R68[医药卫生—骨科学]