中文摘要：

目的 评价脊髓神经元环磷酸腺苷反应元件结合蛋白（CREB）转录共激活因子1（CRTC1）在小鼠骨癌痛维持中的作用.方法 C3H/HeJ雄性小鼠32只,4～6周龄,体重20 ～ 25 g,采用随机数字表法,将其分为4组（n=8）：假手术＋生理盐水组（S组）、骨癌痛＋生理盐水组（BCP组）、骨癌痛＋空白腺病毒载体（Ad-EGFP）组（Ad-EGFP组）和骨癌痛＋CRTC1基因RNA干扰腺病毒（Ad-CRTC1）组（Ad-CRTC1组）.BCP组、Ad-EGFP组和Ad-CRTC1组小鼠在右侧股骨远端骨髓腔接种溶于α-MEM的NCTC2472纤维肉瘤细胞,建立骨癌痛模型,S组小鼠接种不含肿瘤细胞的α-MEM.于接种肿瘤细胞后第14天开始,每天定时分别鞘内注射溶剂生理盐水5μl（BCP组）、溶于生理盐水的Ad-EGFP 5 μl（Ad-EGFP组）和Ad-CRTC1 5μl（Ad-CRTC1组）,连续给药3d,1次/d.于接种前1d、接种后4、7、10、14 d以及鞘内给药结束后1、3、5、7 d（T0-8）时测定机械缩足反应阈和自发抬足次数.结果 与T0时比较,各组T1时机械缩足反应阈降低和自发抬足次数增加（P＜0.05）,S组T2时机械缩足反应阈和自发抬足次数差异无统计学意义（P＞0.05）,BCP组、Ad-EGFP组和Ad-CRTC1组随时间延长机械缩足反应阈降低,自发抬足次数增加（P＜0.05）;与S组比较,其余各组机械缩足反应阈降低,自发抬足次数增加（P＜0.05）;与BCP组和Ad-EGFP组比较,Ad-CRTC1组T5-8时机械缩足反应阈升高,自发抬足次数减少（P＜0.05）.结论 脊髓神经元CRTC1参与了小鼠骨癌痛的维持.

英文摘要：

Objective To evaluate the role of spinal neuronal CREB-regulated transcription coactivator 1 （CRTC1） in the maintenance of bone cancer pain （BCP） in mice.Methods Thirty-two male C3H/HeJ mice,aged 4-6 weeks,weighing 20-25 g,were randomly divided into 4 groups （n =8 each）：sham operation ＋ normal saline group （group S）,BCP ＋ normal saline group （group BCP）,BCP 4＋ empty adenovirus vector Ad-EGFP group （group Ad-EGFP） and BCP ＋ CRTC1 gene RNA interference adenovirus （Ad-CRTC1） group （group Ad-CRTC1）.In BCP,Ad-EGFP and Ad-CRTC1 groups,the model of BCP was established by intramedullary injection of α-minimal essence media containing osteolytic NCTC 2472 cells into the right femur.In group S,the mice were inoculated with α-minimal essence media containing no tumor cells.Normal saline 5 μl,Ad-EGFP 5μl （in normal saline）,and Ad-CRTC1 5 μl （in normal saline） were injected intrathecally in BCP,Ad-EGFP and Ad-CRTC1 groups,respectively,once a day for 3 consecutive days starting from day 14 after inoculation of the tumor cells.On 1 day before inoculation,on 4,7,10 and 14 days after inoculation and on 1,3,5 and 7 days after intrathecal injection （T0-s）,the mechanical paw withdrawal threshold （MWT） and spontaneous lifting times were measured.Results Compared with the baseline value at T0,MWT was significantly decreased,and the spontaneous lifting times were increased at T1 in each group,no significant change was found in MWT and the spontaneous lifting times at T2 in group S,and MWT was gradually decreased,and the spontaneous lifting times were gradually increased with the prolonging time in BCP,Ad-EGFP and Ad-CRTC1 groups.Compared with group S,MWT was significantly decreased,and the spontaneous lifting times were increased in the other groups.MWT was significantly higher,and the spontaneous lifting times were lower at T5-8 in group Ad-CRTC1 than in BCP and AdEGFP groups.Conclusion Spinal neuronal CRTC1 is involved in the maintenance of BCP in mice.