鞘内注射TDAG8的siRNA对大鼠骨癌痛的缓解作用  

Pain-relieving effect of intrathecal injection of TDAG8 siRNA on rats with bone cancer pain

作　　者：殷伟[1] 杭黎华[1] 郑小艳[1] 王丽娜[1] 贾晓明[1] 杨建平[1] 许期年[2] 王秀云[2] 左剑玲[2] 

机构地区：[1]苏州大学附属第一医院麻醉科,江苏苏州215006 [2]苏州大学附属第一医院脑神经研究室,江苏苏州215006

出　　处：《中国药理学通报》2012年第10期1402-1406,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助课题(No 81000479;81171057);江苏省自然科学基金资助课题(No SBK201121879)

摘　　要：目的观察鞘内注射T细胞死亡相关基因8(T celldeath-associated gene 8,TDAG8)的小干扰RNA(small inter-fering RNA,siRNA)对骨癌痛大鼠机械性痛觉过敏以及脊髓TDAG8表达的影响。方法通过将Walker256肿瘤细胞接种在大鼠左侧胫骨骨髓腔内建立骨癌痛模型。观察接种肿瘤前后大鼠机械缩爪反射阈值(paw withdrawl threshould,PWT)和脊髓TDAG8表达水平的变化;并进一步观察痛觉过敏形成后鞘内注射TDAG8的siRNA对大鼠PWT和脊髓TDAG8表达的影响。结果大鼠接种肿瘤后6～18 d,PWT明显下降(P<0.01),脊髓TDAG8的表达明显升高(P<0.01);与对照组相比,鞘内注射siRNA的骨癌痛大鼠,其PWT明显增高(P<0.05),脊髓TDAG8表达水平明显降低(P<0.01)。结论脊髓部位的TDAG8可能参与了大鼠骨癌痛的形成和发展,鞘内注射其siRNA可以通过干扰脊髓TDAG8的表达而具有疼痛缓解作用。Aim To observe the effect of intrathecal injection of T cell death-associated gene 8（TDAG8） small interfering RNA（siRNA） on mechanical hyperalgesia and spinal TDAG8 expression in bone cancer pain rats.Methods Walker256 mammary gland carcinoma cells were inoculated into the rat’s tibia medullary cavity to establish the bone cancer pain model.The change of the paw withdrawl thresthold（PWT） and the expression level of spinal TDAG8 in rats at pre-and post-inoculation,and the effect of intrathecal injection of siRNA on TDAG8 expression and mechanical hyperalgesia were observed.Results From the 6th to 18th day post-inoculation,PWT decreased significantly（P 0.01）,and spinal TDAG8 expression levels progressively reduced（P 0.01）.TDAG8 expression levels in the spinal cord of those bone cancer pain rats injected with small interfering RNA pool were lower,and PWT was higher,compared to the control groups（P 0.01）.Conclusion These results indicate that spinal TDAG8 may be involved in the development of bone cancer pain,and intrathecal siRNA injection may have pain relieving effect through interference with spinal TDAG8 expression.

关 键 词：大鼠 肿瘤 脊髓 鞘内注射 T细胞死亡相关基因8 痛觉过敏 

分 类 号：R332[医药卫生—人体生理学] R322.813[医药卫生—基础医学]