鞘内注射Roscovitine对小鼠骨癌痛行为学的影响  

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

作　　者：张睿[1] 马正良[1] 梅凤美[1] 张娟[1] 顾晓萍[1] 

机构地区：[1]江苏省麻醉学重点实验室,徐州221002

出　　处：《国际麻醉学与复苏杂志》2010年第2期111-114,共4页International Journal of Anesthesiology and Resuscitation

基　　金：江苏省“兴卫工程”医学重点人才课题资助项目（RC2007012）;江苏省卫生部资助项目（WKJ2006-2-8）

摘　　要：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14d＋溶媒）、C组（接种后14d＋溶媒）、R组（接种后14d＋Roscovitine），每组8只。C组和R组将含2×10^5个纤维肉瘤NCTC2472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14d，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DMSO5μl。观察给药前及给药后1、6、24、48、72h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 lateBev，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Roscovitine20μg后6hPMWT（O．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。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 roscovifine （group R） was injected in 14 post 4replanted 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 PMWT [ （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.

关 键 词：细胞周期依赖性激酶5 骨癌痛 ROSCOVITINE 

分 类 号：R738[医药卫生—肿瘤]