中文摘要：

目的评价鞘内注射驱动蛋白17竞争性小肽抑制剂RC-13对骨癌痛小鼠的镇痛效果。方法雄性C3H／HeJ小鼠40只，6～8周龄，体重20。25g，采用随机数字表法，将其随机分为5组（n=8）：假手术组（S组）、骨癌痛＋5μlDMSO组（Ro组）、骨癌痛＋2．5μgRC-13组（R．组）、骨癌痛＋5μg RC—13组（R组）和骨癌痛＋10愕RC-13组（R3组）。‰组、R1组、R2组和R3组小鼠右侧股骨骨髓腔内注射含约2×105个纤维肉瘤细胞的20μla．MEM以制备骨癌痛模型。骨癌痛各组于接种肿瘤细胞后第14天开始，每天定时分别鞘内注射10％DMSO5μl和溶于10％DMSO的RC-132．5μg／5μ1、5μg，5μg、10μg，5μl，连续3d，每天1次。各组于接种前1d、接种后3、5、7、10、14d时测定小鼠机械缩足阈值和自发抬足次数，R0～3组在给药结束后1、3、5和7d时行相同行为学测定。结果与S组比较，其余组接种后7～14d时小鼠机械缩足阈值降低，自发抬足次数增加（P〈0．05）；与R11组比较，R2组给药结束后1d、R2组1和3d、R3组1、3、5d时机械缩足阈值升高，自发抬足次数减少（P〈O．05）；与R1组比较，R2组给药结束后3d、R1组1、3、5d时机械缩足阈值升高，自发抬足次数减少（P〈0．05）；与R组比较，R2组给药结束后1和3d时机械缩足阈值升高，自发抬足次数减少（P〈O．05）。结论鞘内注射驱动蛋白17竞争性小肽抑制剂RC-13对骨癌痛小鼠具有良好的镇痛效果，其效应呈剂量依赖性。

英文摘要：

Objective To investigate the analgesic efficacy of intrathecal injection of RC-13, a competi- tive kinesin superfamily protein 17 antagonist, in a mouse model of bone cancer pain. Methods Forty male C3H/HeJ mice, aged 6-8 weeks, weighing 20-25 g, were randomly divided into 5 groups （ n = 8 each） ： sham op- eration group （group S）; bone cancer pain ＋ ＇5 kd dimethyl sulfoxide （DMSO） group （group Ro ）; bone cancer pain ＋ 2.5 /~g RC-13 group （group Ri ）; bone cancer pain ＋ 5 ttg RC-13 group （group R2 ） and bone cancer pain ＋ 10 /~g RC-13 group （group R3 ） . In groups Ro.3 , bone cancer pain was induced by implantation of ct-min- imal essence medium （a-MEM） containing osteosarooma NCTC 2472 cells into the intramedullary space of right fe- mur. In group S, culture medium ct-MEM containing no cancer cell was injected instead. 10% DMSO 5 $1 and RC-13 2.5 ~g/5 /~1, 5 ttg/5 /11 and 10 ttg/5 ttl dissolved in 10% DMSO were injected intrathecally in groups Ro_s , respectively, once a day for 3 consecutive days starting from 14th day after inoculation of the tumor ceils. Pain be- havior was assessed by the paw withdrawal mechanical threshold （PWMT） and spontaneous lifting times （SLTs） measured at 1 day before inoculation and at 3, 5, 7, 10, 14 days after inoculation. The same tests were also performed at 1, 3, 5 and 7 days after administration in groups R0.3 . Results Compared with group S, PWMT was significantly decreased and SLTs were increased at 7-14 days after inoculation in the other groups （ P 〈 0.05 ）. Compared with group Ro , PWMT was significantly increased and SLTs were reduced at 1 day after administration in group Ri , at 1 and 3 days after administration in group R2, and at 1, 3 and 5 days after administration in group R3 （ P 〈 0.05 ） . Compared with group Ri , PWMT was significantly increased and SLTs were reduced at 3 days after administration in group R2 , and at 1, 3 and 5 days after administration in group R3 （ P 〈 0.05）. Compared with gro