鞘内注射Roscovitine对小鼠骨癌痛行为学的影响

目的 探讨鞘内给予细胞周期依赖性激酶5(cyclin-dependent kinases,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 小鼠采用随机数字表法随机分为3组,S组(假手术后14 d+溶媒)、C组(接种后14d+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)20μl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20μg Roscovitine的二甲基亚砜(DMSO)5μl,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(paw uithdrawal mechanical threshold,PMWT)和热缩足潜伏期(Paw withdrawal thermal latency,PWTL).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7 d,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10 d,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Roscovitine 20μg后6 h 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,12 h达最大值,后逐渐降低,72 h降低到C组水平.结论 鞘内注射Roscovitine可有效缓解小鼠骨癌痛.

Influences of intrathecal administration of roscovitine on bone cancer pain in mouse models

Objective To investigate the influences of intrathecal administration of roscovitine on bone cancer pain in mouse models. Methods Twenty four C3H/Hej mice were divided randomly into group S(sham + vehicle ), group C(tumor + vehicle) or group R (tumor+ roscovitine) (n = 8 ). Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of mice to make bone cancer pain models. α-MEM (group Sand group C) or roscovitine (group R) was injected in 14 post-implanted day. Pain behaviors such as paw withdrawal mechanical threshold(PMWT) and paw withdrawal thermal latency (PWTL) were observed at 1,6, 24,48 and 72 post-injective hour, respectively. Results The level of PMWT and PTWL among every group had no difference before operation. At day 7 after inoculation, PMWT of group 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 PM WT [ (0.70±0.19 ) g ] and PTWL [ ( 14.16±1.07 ) s] increased compared with group C and base level at 6 h after intrathecal administration of 20 μg Roscovitine, and kept increasing until reaching maximum level after 12 h, then the value decreased gradually, lowering to the level of group C after 72 h. Conclusion Intrathecal administration of roscovitine can relief bone cancer pain in mouse models.