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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。
Objective To observe the effects of intrathecal injection of small inter-fering RNA (siRNA) targeting T cell death-associated gene 8 (TDAG8) on mechanical hyperalgesia and TDAG8 expression in spinal cord in painful rats . Methods The model of bone cancer pain was established by inoculating Walker256 tumor cells into the left tibial bone marrow of rats. The changes of paw withdrawl threshould (PWT) and TDAG8 expression in spinal cord were observed before and after tumor inoculation. The effect of intrathecal TDAG8 siRNA on the expression of TDAG8 in PWT and spinal cord was further observed after hyperalgesia. Results Compared with the control group, the intratumoral injection of siRNA for bone cancer pain rats showed that PWT decreased significantly (P <0.01) and the expression of TDAG8 in spinal cord increased significantly (P <0.01) The PWT was significantly increased (P <0.05), and the expression of TDAG8 in spinal cord was significantly decreased (P <0.01). Conclusion TDAG8 in the spinal cord may be involved in the formation and development of bone cancer pain in rats. Intrathecal injection of siRNA may have a pain relief effect by interfering with the expression of TDAG8 in the spinal cord.