中文摘要：

目的 探讨鞘内注射CLP257对大鼠骨癌痛的影响.方法 成年雌性SD大鼠40只,体重180～ 200 g,采用随机数字表法分成4组（n=10）：假手术组（S组）、骨癌痛组（BCP组）、二甲基亚砜组（DMSO组）和CLP257组.采用左侧胫骨干骺端骨髓腔内注射Walker256肿瘤细胞混悬液（约1×10^5个）10μl的方法制备骨癌痛模型.于造模后第7～9天,DMSO组鞘内注射5％二甲基亚砜10μl,1次/d.CLP257组鞘内注射10 μg/μl CLP257 10μl,1次/d.于造模前1天（T0）、造模后第1～6天（T1-6）、造模后第7～9天鞘内给药后4h（T7～9）时测定机械痛阈.于最后1次鞘内给药后,取脊髓组织,分别采用Western blot法和实时荧光定量PCR法测定K^＋-C1-共转运体2（KCC2）及其mRNA的表达.结果 与S组比较,BCP组和DMSO组机械痛阈降低,脊髓KCC2及其mRNA表达下调,CLP257组机械痛阈降低（P＜0.05）,脊髓KCC2及其mRNA表达差异无统计学意义（P＞0.05）;与BCP组比较,CLP257组机械痛阈升高,脊髓KCC2及其mRNA表达上调（P＜0.05）,DMSO组上述指标差异无统计学意义（P＞0.05）.结论 鞘内注射CLP257可减轻大鼠骨癌痛.

英文摘要：

Objective To investigate the effect of intrathecal CLP257 on the bone cancer pain in rats.Methods Forty adult female Sprague-Dawley rats,weighing 180-200 g,were divided into 4 groups （n=10 each） using a random number table：sham operation group （group S）,bone cancer pain group （group BCP）,dimethyl sulfoxide （DMSO） group,and CLP257 group.Bone cancer pain was induced by inoculating Walker 256 mammary gland carcinoma cell suspension （about 1× 10^5cells） 10 μl into the medullary cavity of the left tibia.On 7th-9th days after establishment of the model,5% DMSO 10 μl was injected intrathecally once a day in group DMSO,and 10 μg/μl CLP257 10 μl was injected intrathecally once a day in group CLP257.The mechanical paw withdrawal threshold （MWT） was measured on 1 day before establishment of the model （T0）,on 1st-6th days after establishment of the model （T1-6）,and at 4 h after intrathecal administration on 7th-9th days after establishment of the model （T7-9）.After the last intrathecal administration,the L4-6 segments of the spinal cord were removed for determination of the expression of potassium chloride cotransporter 2 （KCC2） protein and mRNA by Western blot and fluorescent quantitative real-time polymerase chain reaction,respectively.Results Compared with group S,the MWT was significantly decreased,and the expression of KCC2 protein and mRNA was down-regulated in BCP and DMSO groups,and the MWT was significantly decreased （P〈0.05）,and no significant change was found in the expression of KCC2 protein and mRNA in group CLP257 （P〉0.05）.Compared with group BCP,the MWT was significantly increased,and the expression of KCC2 protein and mRNA was up-regulated in group CLP257 （P〈0.05）,and no significant change was found in the parameters mentioned above in group DMSO （P〉0.05）.Conclusion Intrathecal CLP257 can attenuate the bone cancer pain in rats.