Kv1.3钾通道在脑缺血性损伤中的作用机制研究

Kv1.3 potassium channels are mainly expressed in lymphocytes and microglia cells, maintaining resting membrane potential, proliferation and activation of those immune cells. The studies have demonstrated that Kv1.3 channels are increased in the T-cell-mediated autoimmune diseases, and microglia-mediated brain injuries, in which the downregulation of Kv1.3 channels will further prevent the disease progression. How does Kv1.3 function in the ischemic brain injury? Will it produce neuro-protection effect if the Kv1.3 channels are inhibited? The preliminary experiments demonstrated that Kv1.3 blocker significantly decreased infarction area induced by ischemia/reperfusion brain injury and improved nerve function. Therefore to understand the neuroprotection mechanism of Kv1.3 blockers, the present study is going to discuss the role of Kv1.3 potassium channels in the microglia activation by using the following methods, including “middle cerebral artery occlusion” model (MCAO), molecular biology and immunology et al. Therefore the present study would provide theoretical basis for drug target identification and drug development.

Kv1.3钾通道主要表达于淋巴细胞和小胶质细胞，维持免疫细胞静息膜电位，促进免疫细胞增生和活化等。研究证实Kv1.3在T细胞介导的自身免疫性疾病、小胶质细胞介导的多种脑损伤等中功能上调，如抑制通道功能则可抑制炎症反应的进展。那么，Kv1.3钾通道在缺血性脑损伤中的作用如何，该通道功能下调是否具有神经保护作用呢？目前预实验结果表明，Kv1.3选择性阻断剂可显著减小缺血再灌注模型脑梗死的面积并改善神经功能。故本研究拟采用缺血/再灌注（MCAO）模型、分子生物学及免疫学方法等手段，拟从小胶质细胞激活等方面探讨Kv1.3钾通道在缺血性脑损伤中作用，以试图回答Kv1.3阻断剂的神经保护机制。从而进一步为药物靶点确认和新药研发提供理论依据。

Kv1.3钾通道主要表达于免疫细胞，促进免疫细胞增生和活化等。研究证实Kv1.3在T细胞介导的自身免疫性疾病、小胶质细胞介导的多种脑损伤中具有重要的作用。本项目应用两年的时间，探索了Kv1.3钾通道在缺血性脑损伤中的作用。采用缺血/再灌注（MCAO）模型、分子生物学及免疫学方法等手段，从小胶质细胞激活等方面探讨Kv1.3钾通道在缺血性脑损伤中的机制。我们的研究表明，Kv1.3钾通道在脑缺血发生中表达上调，且Kv1.3钾通道阻断剂可显著缓解脑缺血梗死面积。同时还发现Kv1.3阻断剂对脑缺血诱发的小胶质细胞炎性因子的释放具有显著的缓解作用。这些初步研究表明，Kv1.3钾通道在脑缺血发生中具有重要的作用，可能为脑缺血的治疗提供了一个潜在的治疗靶点，为药物发现提供理论依据。