TRPV4-ATP-P2X7通路介导的胶质细胞活化调控神经病理性疼痛的机制

Neuropathic pain seriously affects the quality of social and working lives of patients. Recent studies have found that activation of glial cells plays an important role in the development of neuropathic pain. How to regulate the function of glial cells have become the research hotspot in neuropathic pain. Our previous study found that participation of TRPV4 channel in a signal transduction pathway related with neurons deformation to ATP release. It has been found that ATP can promote the activation of glial cells by binding to P2X7 receptor. While it has not been reported whether TRPV4 channel can induce glial cell activation by regulating P2X7 receptor-dependent signal pathway. Therefore, we hypothesize that TRPV4 channel may regulate the activation of glial cells by regulating P2X7 receptor-dependent signal pathway. In this study, RNA interference, real time-PCR, Western blot, Immunochemistry, ELISA were performed to investigate the hypothesis.

神经病理性疼痛因其严重影响患者的生活与工作质量，成为备受关注的研究对象。近年来的研究发现胶质细胞活化在神经病理性疼痛的发生发展中具有重要作用。调控胶质细胞的功能已成为目前神经病理性疼痛的研究热点。我们前期的研究发现TRPV4通道在参与神经元介导的疼痛信号转导的过程中可促进神经元释放ATP。ATP作为神经递质已被证实可通过与P2X7受体结合促进胶质细胞活化。但TRPV4通道是否可通过ATP-P2X7信号通路调控胶质细胞活化，目前国内外尚未见报道。为此，我们提出假设：TRPV4通道可能通过ATP-P2X7信号通路调控胶质细胞的活化。为了验证这一假说，我们将采用RNA干扰、Western blot、IC、BrdU、ELISA等方法，从原代细胞、组织和动物水平等多方面进行实验设计，拟挖掘TRPV4通道和胶质细胞活化的关系，并以ATP/P2X7为靶点，探索其可能机制，为治疗神经病理性疼痛提供新理论。