CCL2及其受体CCR2在臂丛神经根性撕脱伤诱发神经病理性痛中的作用  

Role of CCL2 and its receptor CCR2 in neuropathic pain induced by brachial plexus root avulsion injury

作　　者：赵睿 鲜航 史林 田通 丛锐 Zhao Rui;Xian Hang;Shi Lin;Tian Tong;Cong Rui(Department of Orthopedics,the First Affiliated Hospital of the Air Force Medical University,Xi′an 710032,China)

机构地区：[1]空军军医大学第一附属医院骨科,西安710032

出　　处：《中华手外科杂志》2021年第2期129-134,共6页Chinese Journal of Hand Surgery

基　　金：国家自然科学基金资助项目(81501064)。

摘　　要：目的探讨趋化因子配体2(chemokine C-C motif ligand 2,CCL2)及其受体在臂丛神经根性撕脱伤(brachial plexus avulsion,BPA)诱发神经病理性痛(neuropathic pain,NP)中的作用机制。方法将30只大鼠随机分为空白对照组(sham)、BPA-NP模型+生理盐水组、BPA-NP模型+CCR2抑制剂组、BPA-NP模型+JAK抑制剂组、BPA-NP模型+NR2B抑制剂组。建立大鼠臂丛神经下干撕脱伤(BPA-NP)模型,分别检测各组大鼠颈8-胸1节段脊髓背角区域CCL2及其受体CCR2的表达。同时通过Western Blot检测各组大鼠颈8-胸1节段脊髓背角区域CCL2、CCR2、NR2B的表达。结果BPA-NP模型+生理盐水组大鼠颈8-胸1节段脊髓背角CCL2及CCR2的荧光定量及蛋白表达量较BPA-NP模型+CCR2抑制剂干预组及空白对照组显著升高,差异具有统计学意义;加入CCR2、JAK及NR2B抑制剂并不能完全抑制CCL2及CCR2的表达,也不能完全抑制NR2B的表达。结论外伤因素会导致BPA-NP大鼠颈8-胸1节段脊髓背角CCL2表达增高,进而与其受体CCR2结合通过激活下游JAK/STAT信号通路但并非唯一通路引起NMDA受体NR2B表达上调,增强中枢敏化作用导致NP的发生。CCL2-JAK/STAT-NMDA通路可能是BPA诱发NP的机制之一。Objective To investigate the mechanism of chemokine(C-C motif)ligand 2(CCL2)and its receptors in neuropathic pain(NP)induced by brachial plexus avulsion(BPA).Methods Thirty rats were randomly divided into 5 groups,including blank control group(sham),BPA-NP model+saline group,BPA-NP model+CCR2 inhibitor group,BPA-NP model+JAK inhibitor group and BPA-NP model+NR2B inhibitor group.The model of brachial plexus lower trunk avulsion injury(BPA-NP)in rats.The expression of CCL2 and its receptor CCR2 in the spinal dorsal horn of C8 to T1 segment were detected.Western blot was used to detect the expression of CCL2,CCR2 and NR2B in the spinal dorsal horn of C8 to T1 segment.Results Compared with BPA-NP model+CCR2 inhibitor intervention group and blank control group,the immunofluorescence quantification and protein expression of CCL2 and CCR2 in the spinal dorsal horn of C8 to T1 segment of BPA-NP model+saline group were significantly increased,which was statistically significant;the addition of CCR2,Jak and NR2B inhibitors could not completely inhibit the expression of CCL2 and CCR2,nor the expression of NR2B completely.Conclusion The traumatic factors can increase the expression of CCL2 in the spinal dorsal horn of C8 to T1 segment of BPA-NP rats,and then CCL2 can be combined with its receptor CCR2 through activating the downstream JAK/STAT signal pathway,but not the only one,which can up-regulate the expression of NMDA receptor NR2B,enhance the central sensitization and lead to the occurrence of NP.CCL2-JAK/STAT-NMDA pathway may be one of the mechanisms of NP induced by BPA.

关 键 词：臂丛 大鼠 根性撕脱伤 神经病理性痛 JAK/STAT信号通路 

分 类 号：R651.3[医药卫生—外科学]