摘要
目的探讨腹腔注射大麻素受体(cannabinoid receptor,CB)2激动剂对骨癌痛大鼠脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白(phosphorylated cyclic AMP respons eclement binding protein,pCREB)表达的影响。方法运用随机数字表法将63只雌性SD大鼠分为3组:肿瘤给药组(J组,15只)、肿瘤对照组(D组,24只)和假手术对照组(S组,24只)。J组、D组的大鼠左侧胫骨上端骨髓腔被注入5μl Walker256大鼠乳腺癌细胞制备骨癌痛模型;S组则注入等量的生理盐水。在造模后第10天,J组腹腔注射JWH-015(100μg/500μ1),D组、s组注射等量JWH-015溶剂二甲基亚砜(dimethylsulfoxide,DMSO)。每组大鼠于造模前1d,造模后4、7、10d,腹腔注射后2、6、24、48、72h,检测手术侧机械刺激缩足阈值(paw withdrawal mechanical threshold,pwMT)和行走痛行为学评分。D组和S组大鼠于造模后4、7d,J组、D组和S组大鼠于造模后10d及腹腔注射后6、24、72h,取脊髓腰膨大进行免疫印迹分析。结果与S组比较,J组和D组大鼠造模后7d PWMT开始降低(P〈0.05),造模后10d行走痛行为学评分增加(P〈0.05),脊髓背角pCREB表达水平于7、10d上调(P〈0.05).与D组比较,腹腔注射JWH-015后24h,J组PWMT(8.7±1.6)g显著上升(P〈0.05),行走痛行为学评分(1.0±0.6)分和pCREB的表达(0.56±0.10)明显下降(P〈0.05)。结论腹腔注射JWH-015可能通过下调脊髓背角pCREB的表达改善骨癌痛大鼠的痛行为。
Objective To investigate the change of phosphorylated cyclic AMP response element binding protein (pCREB) in spinal dorsal horn in a rat model of bone cancer pain, after intraperitoneal injection JWH-015. Methods Sixty-three female SD rats were randomly divided into 3 group: medication administration of JWH-015 group (group J, n=15 ), medication administration of dimethylsulfoxide (DMSO) group (group D, n=l5) and sham group (group S, n=21 ). Group J, D: 5 μl Walker256 breast cancer cells of rat were implanted into the intramedullary space of the left tibia of rat to induce ongoing bone cancer pain model, rats of group S were implanted 5 μ1 NS. On 10 d after implantation, JWH-015 (100 μg/500 μl) was injected into rats of group J, and DMSO was injected into rats of group D and S. The paw withdrawal mechanical threshold(PWMT) and ambulatory pain of each group were detected on 1 d before implantation, and 4, 7, 10 d after implantation, and 2, 6, 24, 48, 72 h after injection . Then, Lumbar intumescentia of rat were taken out to analyze Western-blotting at 4, 7 d after implantation of group D and S, 10 d after implantation, 6, 24, 72 h after injection of group J, D, S. Results Compared with group S, at day 7 after the implantation, the PWMT of group J and D were significantly decreased (P〈O.05), at day 10 after the implantation, the ambulatory pain of group J and D were obviously increased. The expression of pCREB in spinal dorsal horn were up-regulated at day 7 and 10 (P〈0.05). Compared with group D, 24 h after injection, the rat of group J showed remarkable rising of PWMT (8.7±1.6) g and reducing of ambulatory pain (1.0±0.6) and the expression of pCREB (0.56±0.10) (P〈0.05). Conclusions Iintraperitoneal injection JWH-015 attenuated bone cancer pain. which mav be acted via down-regulating the exnression of nCREB in sninnl dorsal hnrn.
出处
《国际麻醉学与复苏杂志》
CAS
2014年第10期882-885,共4页
International Journal of Anesthesiology and Resuscitation
基金
国家自然科学基金(81171048)
国家自然科学基金(81070892)
关键词
大麻素受体
骨癌痛
大鼠
磷酸化环磷酸腺苷反应元件结合蛋白
Cannabinoid receptor
Bone cancer pain
Rat
Phosphorylated cyclic AMP response element binding protein