中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2013年
25期
1997-2000
,共4页
卢波%姚娟%雷卫平%肖纯%孙建良
盧波%姚娟%雷衛平%肖純%孫建良
로파%요연%뢰위평%초순%손건량
受体趋化因子%细胞外信号调节激酶类%小神经胶质细胞%神经痛
受體趨化因子%細胞外信號調節激酶類%小神經膠質細胞%神經痛
수체추화인자%세포외신호조절격매류%소신경효질세포%신경통
CX3CR1%Extracellular signal-regulated protein kinase 5%Microglia%Neuropathic pain
目的 探讨脊髓小胶质细胞CX3CR1/ERK5信号通路在神经病理性疼痛中的作用.方法 建立脊神经结扎(SNL)疼痛模型,检测大鼠脊髓p-ERK5表达的改变及其表达的细胞类型.鞘内注射ERK5反义寡核苷酸,观察抑制脊髓ERK5表达对SNL大鼠PWT与TWL的影响,以确定ERK5在神经病理性疼痛中的作用.SNL大鼠鞘内注射CX3CR1中和抗体,观察阻断该受体对ERK5活化的影响；鞘内注射CX3CR1的配体CX3CL1,观察CX3CL1能否激活脊髓小胶质细胞和ERK5,以及预先抑制ERK5表达能否逆转CX3CL1的作用,以判定神经病理性疼痛条件下CX3CR1对ERK5的调节作用.结果 与假手术组相比,SNL大鼠术后脊髓p-ERK5免疫反应阳性细胞表达增加(61.75±11.52比2.2±0.12; 58.01 ±10.45比1.1 ±0.11)(P＜0.05),荧光双标结果表明p-ERK5主要表达于小胶质细胞.抑制脊髓ERK5表达有效缓解SNL所致的热(13.48±2.0)s比(18.0±3.7)s;(11.6 ±2.3)s比(17.7 ±1.4)s(P＜0.05)与机械(15.42 ±3.46)g比(22.7±3.2)g；(13.6±2.9)g比(21.4±4.1)g痛敏(P＜0.05).与对照组相比,阻断CX3CR1可有效减少SNL大鼠脊髓ERK5的活化(30±9)比(58±12)；(50±12)比(36±4)(P＜0.05).抑制脊髓ERK5的表达缓解鞘内注射CX3CL1所致痛觉过敏与小胶质细胞活化.结论 在神经病理性疼痛条件下,CX3CL1/CX3CR1通过激活脊髓小胶质细胞ERK5,调节脊髓小胶质细胞的活化,该通路参与了脊髓疼痛信号的转导过程.
目的 探討脊髓小膠質細胞CX3CR1/ERK5信號通路在神經病理性疼痛中的作用.方法 建立脊神經結扎(SNL)疼痛模型,檢測大鼠脊髓p-ERK5錶達的改變及其錶達的細胞類型.鞘內註射ERK5反義寡覈苷痠,觀察抑製脊髓ERK5錶達對SNL大鼠PWT與TWL的影響,以確定ERK5在神經病理性疼痛中的作用.SNL大鼠鞘內註射CX3CR1中和抗體,觀察阻斷該受體對ERK5活化的影響；鞘內註射CX3CR1的配體CX3CL1,觀察CX3CL1能否激活脊髓小膠質細胞和ERK5,以及預先抑製ERK5錶達能否逆轉CX3CL1的作用,以判定神經病理性疼痛條件下CX3CR1對ERK5的調節作用.結果 與假手術組相比,SNL大鼠術後脊髓p-ERK5免疫反應暘性細胞錶達增加(61.75±11.52比2.2±0.12; 58.01 ±10.45比1.1 ±0.11)(P＜0.05),熒光雙標結果錶明p-ERK5主要錶達于小膠質細胞.抑製脊髓ERK5錶達有效緩解SNL所緻的熱(13.48±2.0)s比(18.0±3.7)s;(11.6 ±2.3)s比(17.7 ±1.4)s(P＜0.05)與機械(15.42 ±3.46)g比(22.7±3.2)g；(13.6±2.9)g比(21.4±4.1)g痛敏(P＜0.05).與對照組相比,阻斷CX3CR1可有效減少SNL大鼠脊髓ERK5的活化(30±9)比(58±12)；(50±12)比(36±4)(P＜0.05).抑製脊髓ERK5的錶達緩解鞘內註射CX3CL1所緻痛覺過敏與小膠質細胞活化.結論 在神經病理性疼痛條件下,CX3CL1/CX3CR1通過激活脊髓小膠質細胞ERK5,調節脊髓小膠質細胞的活化,該通路參與瞭脊髓疼痛信號的轉導過程.
목적 탐토척수소효질세포CX3CR1/ERK5신호통로재신경병이성동통중적작용.방법 건립척신경결찰(SNL)동통모형,검측대서척수p-ERK5표체적개변급기표체적세포류형.초내주사ERK5반의과핵감산,관찰억제척수ERK5표체대SNL대서PWT여TWL적영향,이학정ERK5재신경병이성동통중적작용.SNL대서초내주사CX3CR1중화항체,관찰조단해수체대ERK5활화적영향；초내주사CX3CR1적배체CX3CL1,관찰CX3CL1능부격활척수소효질세포화ERK5,이급예선억제ERK5표체능부역전CX3CL1적작용,이판정신경병이성동통조건하CX3CR1대ERK5적조절작용.결과 여가수술조상비,SNL대서술후척수p-ERK5면역반응양성세포표체증가(61.75±11.52비2.2±0.12; 58.01 ±10.45비1.1 ±0.11)(P＜0.05),형광쌍표결과표명p-ERK5주요표체우소효질세포.억제척수ERK5표체유효완해SNL소치적열(13.48±2.0)s비(18.0±3.7)s;(11.6 ±2.3)s비(17.7 ±1.4)s(P＜0.05)여궤계(15.42 ±3.46)g비(22.7±3.2)g；(13.6±2.9)g비(21.4±4.1)g통민(P＜0.05).여대조조상비,조단CX3CR1가유효감소SNL대서척수ERK5적활화(30±9)비(58±12)；(50±12)비(36±4)(P＜0.05).억제척수ERK5적표체완해초내주사CX3CL1소치통각과민여소효질세포활화.결론 재신경병이성동통조건하,CX3CL1/CX3CR1통과격활척수소효질세포ERK5,조절척수소효질세포적활화,해통로삼여료척수동통신호적전도과정.
Objective To explore the role of spinal microglial CX3CR1/ERK5 pathway in the development of neuropathic pain.Methods The model of spinal nerve ligation (SNL) was established by ligating the L5 spinal nerve with 6-0 silk thread in male Sprague Dawley rats.The expression of activated ERK5 (p-ERK5) was examined by immunohistochemistry test.To detect the role of ERK5 in neuropathic pain,PWT and PWL were measured after an intrathecal knockdown of ERK5.For determining the regulating effect of CX3CL1/CX3CR1 on the activity of microglial ERK5,CX3CR1 was blocked by an intrathecal injection of anti-rat CX3CR1 antibody and the activity of spinal ERK5 tested.Then whether an intrathecal knockdown of ERK5 could reverse the effect of CX3CL1 on pain hypersensitivity and microglia activation was investigated.Results ERK5 was activated in spinal microglia after SNL compared to the sham group (61.75 ± 11.52 vs 2.2 ±0.12; 58.01 ± 10.45 vs 1.1 ±0.11).The knockdown of ERK5 by an intrathecal injection of antisense oligonucleotides suppressed the mechanical (15.42 ± 3.46 vs 22.7 ± 3.2g; 13.6± 2.9 vs 21.4 ± 4.1 g) and thermal hyperalgesia (13.48 ± 2.0) vs (18.0 ± 3.7) s ; (1 l.6 ± 2.3) vs (17.7 ± 1.4) s induced by nerve injury.The blockage of CX3CR1,a receptor of CX3CL1,significantly reduced the level of ERK5 activation followingSNL (30±9) vs (58±12);(50±12) vs (36±4) (P＜0.05).In addition,the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation.Conclusion CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through ERK5.
