CAJ | 학술논문

目的探讨脊髓水平N-甲基-D-天冬氨酸受体(N-methyl-D-aspartic acid receptor,NMDAR)-细胞外信号调节蛋白激酶5(extracellular signal-regulated kinase 5,ERK5)信号通路在吗啡依赖大鼠戒断行为中的作用.方法成年雄性SD大鼠96只,体质量200～ 250 g,采用随机数字法,将实验动物随机分为四组(n=24):对照组(A组)、戒断组(B组)、二甲基亚砜(DMSO)组(C组)、MK801组(D组).采用剂量递增法皮下注射吗啡以建立大鼠吗啡依赖模型,第6天上午经腹腔注射纳洛酮,催促戒断症状出现,即建立吗啡戒断模型.采用行为药理学方法结合western blot技术,鞘内注射NMDAR抑制剂MK801,观察其对吗啡依赖大鼠戒断行为、戒断所致痛觉过敏及脊髓p-ERK5表达的影响.结果 A组大鼠腹腔注射纳洛酮后并未出现戒断症状及痛觉过敏.与A组相比,B组大鼠戒断症状评分[(45.2±7.3)分]、痛觉过敏评分[(14.4±3.7)分],C组大鼠戒断症状评分[(44.7±6.2)分]、痛觉过敏评分[(13.2±2.7)分],D组大鼠戒断症状评分[(28.3±1.6)分]、痛觉过敏评分[(5.9±11)分]明显增加(P＜0.05);与C组相比,D组大鼠鞘内注射MK801后戒断症状评分[(28.3±1.6)分]、痛觉过敏评分[(5.9±1.1)分]明显降低(P＜0.05).与A组相比,B组大鼠脊髓水平p-ERK5(12 848±621)、C组大鼠脊髓水平p-ERK5(12 579±396)表达显著上调(P＜0.05);与C组大鼠脊髓水平p-ERK5(12 579±396)相比,D组大鼠鞘内注射MK801后脊髓水平p-ERK5(5123±546)表达显著下调(P＜0.05).结论脊髓水平NMDAR-ERK5信号通路参与吗啡依赖大鼠戒断症状的表达.
목적 탐토척수수평N-갑기-D-천동안산수체(N-methyl-D-aspartic acid receptor,NMDAR)-세포외신호조절단백격매5(extracellular signal-regulated kinase 5,ERK5)신호통로재마배의뢰대서계단행위중적작용.방법 성년웅성SD대서96지,체질량200～ 250 g,채용수궤수자법,장실험동물수궤분위사조(n=24):대조조(A조)、계단조(B조)、이갑기아풍(DMSO)조(C조)、MK801조(D조).채용제량체증법피하주사마배이건립대서마배의뢰모형,제6천상오경복강주사납락동,최촉계단증상출현,즉건립마배계단모형.채용행위약이학방법결합western blot기술,초내주사NMDAR억제제MK801,관찰기대마배의뢰대서계단행위、계단소치통각과민급척수p-ERK5표체적영향.결과 A조대서복강주사납락동후병미출현계단증상급통각과민.여A조상비,B조대서계단증상평분[(45.2±7.3)분]、통각과민평분[(14.4±3.7)분],C조대서계단증상평분[(44.7±6.2)분]、통각과민평분[(13.2±2.7)분],D조대서계단증상평분[(28.3±1.6)분]、통각과민평분[(5.9±11)분]명현증가(P＜0.05);여C조상비,D조대서초내주사MK801후계단증상평분[(28.3±1.6)분]、통각과민평분[(5.9±1.1)분]명현강저(P＜0.05).여A조상비,B조대서척수수평p-ERK5(12 848±621)、C조대서척수수평p-ERK5(12 579±396)표체현저상조(P＜0.05);여C조대서척수수평p-ERK5(12 579±396)상비,D조대서초내주사MK801후척수수평p-ERK5(5123±546)표체현저하조(P＜0.05).결론 척수수평NMDAR-ERK5신호통로삼여마배의뢰대서계단증상적표체.
Objective To investigate the roles of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinases 5 signaling pathway in naloxone-induced withdrawal response in morphine-dependent rats.Methods Ninety-six adult male SD rats weighting 230-250 g were randomly divided into 4 groups:control group,withdrawal group,DMSO group and MK801 group.Rats were subcutaneously injected with morphine.On day 6,rats were injected with naloxone (intraperitoneal) to precipitate morphine withdrawal syndromes.To identify the function of NMDAR-ERK5 signaling pathway in morphine withdrawal,morphine withdrawal-like behavior test and western blot technique were used in this research.The scores of morphine withdrawal symptom,morphine withdrawal-induced allodynia and the activation of ERK5 in spinal cord were observed after intrathecal injection of MK801.Results There was no withdrawal symptoms and withdrawal-induced allodynia in group A after intraperitoneal injection of naloxone.Compared with group A,withdrawal score (45.2±7.3),score of withdrawal-induced allodynia (14.4±3.7) of group B,withdrawal score (44.7±6.2),score of withdrawal-induced allodynia (13.2±2.7) of group C and withdrawal score (28.3±1.6),score of withdrawal-induced allodynia (5.9± 1.1) of group D were significantly increased (P＜ 0.05).Compared with group C,the total withdrawal score (28.3 ± 1.6),score of withdrawal-induced allodynia (5.9± 1.1) of group D were significantly decreased (P＜0.05).Compared with group A,the expression of spinal p-ERK5 of group B (12848±621) and group C (12579±396) were significantly increased (P＜0.05).Compared with group C,the expression of spinal p-ERK5 of group D (5 123±546) was significantly decreased (P＜0.05).Condusion The signaling pathway of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinases 5 contributes to naloxone-induced withdrawal response in morphine-dependent rats.