骨癌痛小鼠脊髓水平CREB转录共激活因子1表达的变化

摘要

Objective To investigate the changes in the expression of CREB-regulated transcription coactivator 1 (CRTC1) in spinal cord during the development and maintenance of bone cancer pain in mice.Methods Forty six male C3H/HeJ mice were randomly divided into Sham group (n=23) and Tumor group (n=23).The mouse model of bone cancer pain was developed by intra-femur inoculation of α-minimal essence media (α-MEM) with osteolytic NCTC 2472 cells.The mice in sham group were inoculated with α-MEM without NCTC 2472 cells.Pain behaviors such as the paw withdrawal mechanical threshold (PWMT) and the number of spontaneous flinches (NSF) were assessed on 1 d before inoculation and on 4 d,7 d,10 d,14 d,21 d after inoculation.At each corresponding time point,three mice of each group were killed just after the pain behaviors assessment and the samples of spinal cord lumbar segment were obtained to detect the expression of CRTC1 using Western Blot.Results Compared with Sham group,PWMT((1.35±0.14) g,(1.10±0.28) g,(0.78±0.25) g,(0.47±0.16) g,(0.34±0.16)g) was significantly decreased (P＜0.05) and NSF((3.12±0.74),(6.02±0.67),(7.42± 1.22),(10.824±0.98),(12.48±1.06)) was significantly increased (P＜0.05) on 7 d,10 d,14 d and 21 d aftcr inoculation in Tumor group.Compared with baseline level,significant increase in the expression of CRTC1 in spinal cord was observed on 4 d in both Sham group and Tumor group (P＜0.05).Compared with baseline level and Sham group,significant increase in the expression of CRTC1 in spinal cord was observed on 7 d,10 d,14 d and 21 d in Tumor group (P＜0.05).Conclusion Expression of CRTC1 in spinal cord is up-regulated in mice with bone cancer pain,and this change may be involved in the development and maintenance of bone cancer pain.%目的 探讨骨癌痛小鼠脊髓水平CREB转录共激活因子1(CRTC1)表达的变化.方法 采用随机数字表法,46只C3H/HeJ雄性小鼠随机分为假手术组(Sham组,n=23)和肿瘤组(Tumor组,n=23),Tumor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,Sham组小鼠接种不含肿瘤细胞的α-MEM.两组在术前1d、术后4d、7d、10 d、14 d、21 d检测痛行为学,并于相应时间点痛行为学检测后,分别随机选取3只小鼠处死,取脊髓L3-L5节段,采用Western Blot法检测CRTC1的蛋白表达水平.结果 与Sham组比较,Tumor组接种后各时间点机械缩足阈值[(1.35±0.14)g,(1.10±0.28)g,(0.78±0.25)g,(0.47±0.16)g,(0.34±0.16)g]明显降低(P＜0.05),自发抬足次数[(3.12±0.74)次,(6.02±0.67)次,(7.42±1.22)次,(10.82±0.98)次,(12.48±1.06)次]明显增加(P＜0.05).与基础值相比,Sham组和Tumor组脊髓水平CRTC1的表达在术后4d升高(P＜0.05);与基础值和Sham组相比,Tumor组脊髓水平CRTC1的表达在术后7d、10d、14d、21 d均升高(P＜0.05).结论 骨癌痛小鼠脊髓水平CRTC1的蛋白表达上调,该变化可能参与了骨癌痛的发生和维持.