长春新碱致神经病理性疼痛模型中胶质细胞及IL1β、GDNF表达的变化.DOCVIP

临床医学论文-长春新碱致神经病理性疼痛模型中胶质细胞及IL1β、GDNF表达的变化 【摘要】? 目的 研究长春新碱致神经病理性疼痛中胶质细胞是否活化及其作用机制。方法 大鼠腹腔内重复注射长春新碱建立模型。免疫化检测脑及脊髓中星形胶质细胞和小胶质细胞特异性活化标志物GFAP和OX42的表达。RTPCR测定IL1β和GDNF mRNA在脊髓腰段的表达。结果 给药大鼠分别在第8 天和第5天出现机械痛阈降低和热痛耐受时间降低。给药大鼠中脑导水管周围灰质及脊髓灰质中见明显胶质细胞的活化。给药组较对照组IL1β表达增加，GDNF表达减少。结论 胶质细胞在长春新碱致神经病理性疼痛中明显活化。IL1β及GDNF与长春新碱引起的神经病理性疼痛有关。 【关键词】? 长春新碱；疼痛；胶质细胞；胶质细胞源性神经营养因子 　　Activation?? of?? Glial Cells? and Expression Change? of? IL1β,GDNF? in Vincristineinduced Neuropathic Pain 　　Abstract：Objective? Glial cells play essential roles in creation and maintenance of pain state. This study was designed to explore the activation of glial cells in vincristineinduced neuropathic　pain, and to find how glial cells influence pain threshold.Methods? We adapted a model by using repeated intraperitoned injection of vincristine. By immunohistochchemical technique, the expression of specific activation markers of astrocytes and microglials, glial fibrillary acidic protein (GFAP) and OX42 respectively, were examined in brain and lumbar intumescentia. Using RTPCR analysis techniques, the expression of interleukine1β(IL1β) and glial cell linederived neurotrophic factor (GDNF) in lumbar intumescentia were tested.Results? Mechanical hyperalgsia appeared on the 8th day and thermal hyperalgsia appeared on the 5th day of vincristine treatment. Glial cells were obviously active in periaquenductal gray and spinal gray. IL1β expression was increased in chemotherapy group, while GDNF was higher in control group.Conclusion? Glial cells were active in Vincristineinduced neuropathic pain. The change of expression of IL1βand GDNF were involved in neuropathic pain evoked by vincristine. 　　Key words：Vincristine;? Pain; Glial cells;? GDNF 　　0? 引言 ??? 长春新碱是常用抗肿瘤药物，也是引起神经病理性疼痛的常见药物之一。近年发现胶质细胞在神经病理性疼痛中起重要作用? [1]。长春新碱引起的神经病理性疼痛中是否有胶质细胞的参与尚不清楚。本研究建立长春新碱致神经病理性疼痛大鼠模型，检测其脑和脊髓腰段胶质细胞的活化，并检测脊髓腰段 IL1β、胶质细胞源性神经营养因子(Glial cell linederived neurotrophic factor, GDNF)的表达变化。探讨长春新碱致神经病理性疼痛的机制，为寻求新的治疗策略提供依据。 　　1? 材料和方法