KCNQ钾通道在糖尿病神经病理性疼痛中的作用及机制研究

发布时间：2018-03-29 11:49

本文选题：神经病理性疼痛　切入点：甲基乙二醛　出处：《中国药理学与毒理学杂志》2016年10期

【摘要】：目的在糖尿病神经病理性疼痛(diabetic neuropathic pain,DNP)发生过程中,KCNQ钾通道所起的作用及其机制。方法首先是在动物整体水平上,建立链脲佐菌素(streptozocin,STZ)诱导的糖尿病模型以及甲基乙二醛(methylglyoxal,MG)诱导的疼痛模型,通过分离背根神经元,检测两种模型离子通道表达变化是否一致,同时检测糖尿病模型中甲基乙二醛的水平。其次是在细胞水平上,观察MG以及MG+MG清除剂对离子通道活性和电流的影响,探讨KCNQ3通道开放剂对DNP的缓解作用以及MG是如何调控离子通道改变的。结果在STZ诱导的模型中,血糖明显升高,机械痛和热痛明显降低,其KCNQ3通道的表达也有明显的降低;同时,在STZ诱导的模型中,MG的浓度是明显升高的,而MG模型中KCNQ3的表达量也是明显下降的。结论 STZ以及MG诱导的模型,均可诱发KCNQ钾通道表达的降低;MG调控KCNQ活性的变化可能通过与离子通道氨基酸反应,调控通道的活性;KCNQ可作为DNP治疗的药理学靶点。
[Abstract]:Objective to investigate the role and mechanism of potassium channel in diabetic neuropathic pain induced by neuropathic. The diabetic model induced by streptozocinine (STZ) and the pain model induced by methylglyoxalen (MG) were established. The changes of ion channel expression in the two models were detected by the separation of dorsal root neurons. The effect of MG and MG scavenger on ion channel activity and current was observed at the cellular level. To investigate the effect of KCNQ3 channel opener on the remission of DNP and how MG regulates the change of ion channel. Results in the model induced by STZ, blood glucose was significantly increased, mechanical pain and heat pain were significantly decreased, and the expression of KCNQ3 channel was also significantly decreased. At the same time, the concentration of KCNQ3 in STZ induced model was significantly increased, and the expression of KCNQ3 in MG model was also decreased. Conclusion STZ and MG-induced model can significantly decrease the expression of KCNQ3. All of them can induce the decrease of KCNQ potassium channel expression and the change of KCNQ activity regulated by MG may be the pharmacological target of DNP therapy by reacting with ion channel amino acids.
【作者单位】：中国医学科学院药物研究所;
【基金】：国家自然科学基金(81470163)
【分类号】：R587.2;R741

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