国际麻醉学与复苏杂志   2010, Issue (2): 111-114
    
鞘内注射Roscovitine对小鼠骨癌痛行为学的影响
张睿 马正良 梅凤美 张娟 顾晓萍1()
1.221002,徐州医学院江苏省麻醉重点实验室
The effects of intrathecal administration of Roscovitine in bone cancer pain of mice
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摘要:

目的 探讨鞘内给予细胞周期依赖性激酶5(CDK5)特异性拮抗剂Roscovitine对小鼠骨癌痛行为学的影响。方法 24只C3H/HeJ小鼠随机分为3组,S组(假手术后14d+溶媒)、C组(接种后14 d+溶媒)、R组(接种后14 d+Roscovitine),每组8只。C组和R组将含2×105个纤维肉瘤NCTC 2472细胞的最小必需培养基(α-MEM)20 μl注射到小鼠右侧股骨远端骨髓腔内,制作骨癌痛模型。S组只注入不含肿瘤细胞的α-MEM。术后14 d,R组小鼠鞘内注射含有20 μg Roscovitine的二甲基亚砜(DMSO)5 μl, C组及S组小鼠鞘内注DMSO 5 μl。观察给药前及给药后1、6、24、48、72 h检测小鼠痛行为学的变化:机械缩足阈值(MWT)和热缩足潜伏期(TWL)。结果 各组术前基础机械缩足阈值及热缩足潜伏期比较差异无统计学意义(P>0.05)。接种后7d,C 组PMWT(1.08±0.24)g,与 S 组(1.85±0.28)g 相比明显降低(P<0.05);接种后 10d,C 组 PTWL(12.7±1.4)s较 S 组(18.6±2.1)s明显缩短(P<0.05),C 组小鼠的痛行为学随时间逐渐加重,与 S 组小鼠比较差异有统计学意义(P<0.05);与C 组及给药前基础值相比,鞘内注射 Roscovitine20 滋g后 6h PMWT(0.70±0.19)g 显著增加(P<0.05),PTWL(14.16±1.07)s 显著延长(P<0.05),并随时间逐渐增加,12h 达最大值,后逐渐降低,72h 降低到C 组水平。结论 鞘内注射Roscovitine可有效缓解小鼠骨癌痛。

关键词: 细胞周期依赖性激酶5;骨癌痛;Roscovitine
Abstract:

Objective The present experiment investigated if intrathecal administration of Roscovitine could affect bone cancer pain in mice. Methods 24 C3H/HeJ mice were divided randomly into group S (sham+ vehicle), group C (tumor+ vehicle) and group R (tumor+ Roscovitine). Every group has eight mice. Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of mice to induce ongoing bone cancer related pain behaviors. The sham group was inoculated by α-MEM without any cells. The mice were observed the changes of pain behaviors in group R, C and S, such as paw withdrawal mechanical threshold (MWT) and paw withdrawal thermal latency (TWL), at 1 , 6 , 24,48,72 h after intrathecal administration of 20 μg Roscovitine or 5 μl DMSO. Results The levelof PMWT and PTWL among every group had no difference before operation. At day7 afterinoculation,PMWTofgroup tumor decreased to(1.08±0.24)g,and at day 10 PTWL shortened to(12.7±1.4)s,and then the pain behaviors of group tumor showed aggravation along with the development of cancer pain. There was significant difference in the pain behavior thresholds between group sham and group tumor(P<0.05). The level of PMWT[(0.70±0.19)g]and PTWL[(14.16±1.07)s]increased compared with group C and base level at 6h after intrathecal administration of 20 μg Roscovitine,and kept increasing until reaching maximum level after 12h,then the value decreased gradually,lowering to the level of group C after 72 h. Conclusion Intrathecaladministration ofroscovitine can relief bone cancer pain in mouse models.

Key words: Cdk5; Cancer pain; Roscovitine