CAJ | 학술논문

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.
목적 평개척수신경원배린산선감반응원건결합단백(CREB)전록공격활인자1(CRTC1)재소서골암통유지중적작용.방법 C3H/HeJ웅성소서32지,4～6주령,체중20 ～ 25 g,채용수궤수자표법,장기분위4조(n=8):가수술+생리염수조(S조)、골암통+생리염수조(BCP조)、골암통+공백선병독재체(Ad-EGFP)조(Ad-EGFP조)화골암통+CRTC1기인RNA간우선병독(Ad-CRTC1)조(Ad-CRTC1조).BCP조、Ad-EGFP조화Ad-CRTC1조소서재우측고골원단골수강접충용우α-MEM적NCTC2472섬유육류세포,건립골암통모형,S조소서접충불함종류세포적α-MEM.우접충종류세포후제14천개시,매천정시분별초내주사용제생리염수5μl(BCP조)、용우생리염수적Ad-EGFP 5 μl(Ad-EGFP조)화Ad-CRTC1 5μl(Ad-CRTC1조),련속급약3d,1차/d.우접충전1d、접충후4、7、10、14 d이급초내급약결속후1、3、5、7 d(T0-8)시측정궤계축족반응역화자발태족차수.결과 여T0시비교,각조T1시궤계축족반응역강저화자발태족차수증가(P＜0.05),S조T2시궤계축족반응역화자발태족차수차이무통계학의의(P＞0.05),BCP조、Ad-EGFP조화Ad-CRTC1조수시간연장궤계축족반응역강저,자발태족차수증가(P＜0.05);여S조비교,기여각조궤계축족반응역강저,자발태족차수증가(P＜0.05);여BCP조화Ad-EGFP조비교,Ad-CRTC1조T5-8시궤계축족반응역승고,자발태족차수감소(P＜0.05).결론 척수신경원CRTC1삼여료소서골암통적유지.
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.