谷氨酸可诱导脊髓星形胶质细胞合成释放IL-6并参与痛觉敏感形成
首发时间:2014-02-24
摘要:目的:活化的星形胶质细胞在慢性疼痛中发挥重要作用。谷氨酸是脊髓内参与痛觉传递和调制的最重要的神经递质,但它对脊髓星形胶质细胞的直接作用并不明确。本研究将探讨谷氨酸对星形胶质细胞功能的影响及其在慢性痛敏形成中的作用。方法:原代培养脊髓星形胶质细胞,谷氨酸孵育后免疫细胞化学方法观察细胞形态,分别用Real-Time PCR法和ELISA方法检测大鼠脊髓星形胶质细胞中IL-6 mRNA的表达水平和IL-6的释放。最后将谷氨酸预先孵育的脊髓星形细胞注入动物脊髓腰膨大部位,观察动物痛行为。结果:谷氨酸孵育后,星形胶质细胞呈现活化态。IL-6的释放从6小时开始明显增加并随时间逐渐上升在24小时达到高峰。IL-6 mRNA水平也呈现相同的趋势。谷氨酸预先孵育的星形胶质细胞可诱发动物的热痛敏。结论:谷氨酸可以直接活化脊髓星形胶质细胞参与热痛觉敏感的形成。谷氨酸激活的星形胶质细胞释放的细胞因子如IL-6可能在热痛觉敏感的形成中发挥重要作用。
关键词: 神经生物学 谷氨酸 痛觉敏感 脊髓星形胶质细胞 IL-6
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Glutamate activated spinal astrocyte are involved in the thermal hyperalgesia by the release of IL-6
Abstract:Objective: Activated glia plays an important role in chronic pain. But how did each stimulus activates glia still has no mechanisms. Glutamate is a significant excitatory transmitter and involved in the spinal pain signal transmission. Whether glutamate could activate astrocytes and participated in chronic pain is still not clear. This study explored whether glutamate can activate astrocytes and activated astrocytes are involved in the thermal hyperalgesia. Methods: Primary cultured spinal astrocytes were incubated with glutamate. The morphologic changes of astrocytes were analyzed by immunocytochemistry. The mRNA expression and release of IL-6 were determined by RT-PCR and ELISA assay respectively to observe the functional changes of astrocyte. The glutamate activated spinal astrocytes were injected intrathecally into the lumber subarachnoid space of rats, paw withdrawal latency (PWL) in response to thermal stimuli was tested. Results: Glutamate stimulation could induce astrocyte reaction. 6 hours after glutamate incubation, the IL-6 release started to increase and reached the peak 24 hours after glutamate stimulation. The mRNA expression of IL-6 had the same tendency. The intrathecally injection of glutamate-stimulated astrocytes induced a dramatic reduction in PWL. The PWL reduction started 2 h after astrocyte injection and lasted for 6 hours. Conclusions: Glutamate can activate astrcytes in vitro. Glutamate activated astrocytes are involved in the thermal hyperalgesia. IL-6 released from glutamate activated astrocytes may play an important role in the thermal hyperalgesia..
Keywords: neurobioloby glutamate hyperalgesia spinal astrocyte IL-6
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谷氨酸可诱导脊髓星形胶质细胞合成释放IL-6并参与痛觉敏感形成
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