CAJ | 학술논문

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 response element 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5μlWalker256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(100 μg/500μl),D组、S组注射等量JWH-015溶剂二甲基亚髓砜(dimethylsulfoxide,DMSO).每组大鼠于造模前1d,造模后4、7、10 d,腹腔注射后2、6、24、48、72 h,检测手术侧机械刺激缩足阈值(paw withdrawal mechanicalthreshold,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10 d及腹腔注射后6、24、72 h,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7 d PWMT开始降低(P＜0.05),造模后10 d行走痛行为学评分增加(P＜0.05),脊髓背角pCREB表达水平于7、10 d上调(P＜0.05).与D组比较,腹腔注射JWH-015后24 h,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.
목적 탐토복강주사대마소수체(cannabinoid receptor,CB)2격동제대골암통대서척수배각린산화배린산선감반응원건결합단백(phosphorylated cyclic AMP response element binding protein,pCREB)표체적영향. 방법 운용수궤수자표법장63지자성SD대서분위3조:종류급약조(J조,15지)、종류대조조(D조,24지)화가수술대조조(S조,24지).J조、D조적대서좌측경골상단골수강피주입5μlWalker256대서유선암세포제비골암통모형;S조칙주입등량적생리염수.재조모후제10천,J조복강주사JWH-015(100 μg/500μl),D조、S조주사등량JWH-015용제이갑기아수풍(dimethylsulfoxide,DMSO).매조대서우조모전1d,조모후4、7、10 d,복강주사후2、6、24、48、72 h,검측수술측궤계자격축족역치(paw withdrawal mechanicalthreshold,PWMT)화행주통행위학평분.D조화S조대서우조모후4、7d,J조、D조화S조대서우조모후10 d급복강주사후6、24、72 h,취척수요팽대진행면역인적분석. 결과 여S조비교,J조화D조대서조모후7 d PWMT개시강저(P＜0.05),조모후10 d행주통행위학평분증가(P＜0.05),척수배각pCREB표체수평우7、10 d상조(P＜0.05).여D조비교,복강주사JWH-015후24 h,J조PWMT(8.7±1.6)g현저상승(P＜0.05),행주통행위학평분(1.0±0.6)분화pCREB적표체(0.56±0.10)명현하강(P＜0.05). 결론 복강주사JWH-015가능통과하조척수배각pCREB적표체개선골암통대서적통행위.
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=15) 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 μl 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＜0.05),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 may be acted via down-regulating the expression of pCREB in spinal dorsal horn.