目的探讨脊髓水平细胞外信号调节蛋白激酶5(extra—cellular signal-regulated protein kinase5,ERK5)在大鼠吗啡戒断行为中的作用。方法成年雄性SD大鼠96只,体质量200~250g,采用随机数字法,将其分为4组(每组n=24):生理盐水一纳洛酮-DMSO组(A组)、生理盐水一纳洛酮一BIX02188组(B组)、吗啡一纳洛酮一DMSO组(C组)、吗啡一纳洛酮一BIX02188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。结合药理学手段鞘内注射ERK5特异性抑制剂BIX02188,观察其对吗啡依赖大鼠戒断行为及戒断所致的痛觉过敏的影响。结果A、B两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,C组大鼠戒断后咬牙(7.5±1.1)分、湿狗样抖动(4.6+0.7)分、戒断后跳跃(5.3+0.7)分、扭体(8.9±I.9)分、腹泻(7.1±1.6)分、流涎(2.8+0.6)分、体质量减轻(7.9+0.9)分、戒断症状总评分(44.8+5.9)分、痛觉过敏评分(14.6±2.4)分及D组大鼠戒断后咬牙(3.1±0.5)分、湿狗样抖动(1.5+0.D)分、戒断后跳跃(2.2+0.5)分、扭体(7.9±1.6)分、腹泻(1.8+0.5)分、流涎(2.8+0.9)分、体质量减轻(3.7±0.6)分、戒断症状总评分(23.1±1.3)分、痛觉过敏评分(3.5±1.1)分明显增加(P〈O.05);与C组相比,D组大鼠鞘内注射BIX02188后戒断症状如咬牙(3.1±0.5)分、湿狗样抖动(1.50.4)分、戒断后跳跃(2.2±0.5)分、腹泻(1.8+0.5)分、体质量减轻(3.70.6)分、戒断症状总评分(23.1±I.3)分、痛觉过敏评分(3.5±1.1)分明显得到缓解(P〈0.05);而扭体(7.9±1.6)分及流涎(2.80.9)分并未得到缓解
Objective To investigate the roles of spinal extracellular signal-regulated protein kinases 5 (ERK5) on morphine withdrawal in rats. Methods Ninety-six male and adult SD rats weighting 230-250 g were randomly divided into saline-naloxone-DMSO group (group A) , saline-naloxone-BIX02188 group (group B) , mor- phine-naloxone-DMSO group (group C) and morphine-naloxone-BIX02188 group (group D). To set up morphine dependent model ,rats were subcutaneously injected with morphine in the increasing dosage method. On day 6,4 h after the injection of morphine, rats were injected with naloxone (intraperitoneal) to precipitate morphine withdraw- al syndrome. The scores of morphine withdrawal symptom and morphine withdrawal-induced allodynia were ob- served after intratheeal injection of ERK5 inhibitor BIX02188. Result There were not withdrawal symptoms and withdrawal-induced allodynia in group A and B after intraperitoneal injection of naloxone. Compared with group A, teeth chatting ( 7.5 ~ 1.1 ), wet dog shacks ( 4.6 ± 0.7 ), jump ( 5.3 ± 0.7 ), abnormal position ( 8.9 ± 1.9 ), diarrhea ( 7.1 ± 1.6 ) , salivation ( 2.8 ± 0.6 ), weight loss ( 7.9 ± 0.9 ) , total withdrawal score ( 44.8 ± 5.9 ), score of withdrawal- induced allodynia (14.6±2.4) of group C and teeth chatting ( 3.1 ±0.5), wet dog shacks ( 1.5±0.4), jump ( 2.2± 0.5 ), abnormal position ( 7.9± 1.6), diarrhea ( 1.8±0.5 ), salivation ( 2.8±0.9), weight loss ( 3.7±0.6), total with- drawal score ( 23.1 ± 1.3) and score of withdrawal-induced allodynia ( 3.5 ± 1.1 ) of group D were significantly in- creased (P〈0.05). Compared with, group C ,teeth chatting (3.1~0.5) ,wet dog shacks (1.5±0.4) ,jump (2.2~0.5) ,diarrhea (1.8-±0.5) ,weight loss (3.7~0.6) and total withdrawal score (23.1~1.3),score of withdrawal-induced allodynia (3.5~ 1.1) of group D were significantly decreased (/o〈0.05). But there was not significant cha