中国药理学与毒理学杂志2025，Vol.39Issue(6)：401-411,11.DOI:10.3867/j.issn.1000-3002.2025.07985
钾通道Kv1.3介导创伤性脑损伤后神经功能障碍及神经炎症
Potassium channel Kv1.3 mediates neurodysfunction and neuroin-flammation after traumatic brain injury
摘要
Abstract
OBJECTIVE To investigate the effects of potassium channel Kv1.3knockout(Kv1.3 KO)on neurological dysfunction and neuroinflammation in C57BL/6 mice following traumatic brain injury(TBI).METHODS C57BL/6 mice and homozygous Kv1.3 KO C57BL/6 mice were subjected to the classic controlled cortical impact model to establish a TBI model.The experimental groups included the sham surgery group,C57BL/6 TBI model group(TBI group),and a Kv1.3 KO C57BL/6 TBI model group(TBI+Kv1.3 KO group).At 1,2,and 3 weeks post-modeling,real-time quantitative PCR was used to measure the mRNA expression levels of Kv1.3,interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and IL-10 in hippocampal tissues.At 1 and 3 weeks post-modeling,Western blotting was performed to detect Kv1.3 protein expressions in the hippocampus.At 3 weeks post-modeling,Western blotting was used to assess the protein levels of IL-1β,IL-6,TNF-α,and IL-10 in hippocampal tissues.Additionally,immunofluorescence was employed to quantify cells co-labeled with the microglial marker ionized calcium-binding adapter molecule 1(IBA1)and Kv1.3,IL-1β,or TNF-α in the hippocampus.Patch-clamp recordings were conducted to measure Kv1.3 channel currents in primary microglia at 3 weeks post-modeling.Neurological function was evaluated at 1 and 3 weeks post-modeling using the neurological severity score(NSS),pole climbing,and rotarod tests.Cognitive function was assessed at 3 weeks post-modeling via open field,Morris water maze,and Y-maze tests.RESULTS Compared with the sham group,the TBI group exhibited significantly elevated mRNA expression levels of Kv1.3 and IL-1β in the hippocampus at 1,2 and 3 weeks post-modeling,while IL-6 and IL-10 mRNA levels showed no significant changes.Notably,TNF-α mRNA expressions demonstrated a significant increase only at 2 and 3 weeks post-modeling.At 1 and 3 weeks post-modeling,Kv1.3 protein expres-sions in the hippocampus were significantly higher in the TBI group.At 3 weeks post-modeling,hippo-campal IL-1β and TNF-α protein levels were markedly increased in the TBI group,whereas IL-6 and IL-10 protein levels did not change significantly.Moreover,Kv1.3 current density in primary microglia was signifi-cantly enhanced in the TBI group at 3 weeks post-modeling.Immunofluorescence analysis revealed that the number of IBA1-positive microglia co-labeled with Kv1.3,IL-1β,or TNF-α in the hippocampus was significantly larger in the TBI group than in the sham group at 3 weeks post-modeling.Behaviorally,the TBI group exhibited significantly higher NSS scores,lower success rates in full turn attempts,and longer times taken to descend the pole at 1 and 3 weeks post-modeling compared with the sham group.At 3 weeks post-modeling,TBI mice also demonstrated reduced total movement distance in the open field,decreased time spent in the central zone,fewer platform crossings,less time in the target quadrant,and lower spontaneous alternation rates.In contrast,the TBI+Kv1.3 KO group showed signifi-cantly improved outcomes compared with the TBI group:lower NSS scores,higher success rates in full turns,and shorter time taken to descend the pole at 1 and 3 weeks post-modeling.At 3 weeks post-modeling,the TBI+Kv1.3 KO group displayed longer rotarod endurance,increased total movement dis-tance in the open field,more time spent in the central zone,higher platform crossings,greater target quadrant exploration time,and improved spontaneous alternation rates.Furthermore,at 1 and 3 weeks post-modeling,the TBI+Kv1.3 KO group exhibited significantly reduced mRNA expression levels of the inflammatory cytokines IL-1β and TNF-α in the hippocampus compared with the TBI group.CONCLU-SION Potassium channel Kv1.3 knockout mitigates neurological dysfunction and neuroinflammation in C57BL/6 mice following TBI.关键词
创伤性脑损伤/小胶质细胞/钾通道Kv1.3/炎症因子Key words
traumatic brain injury/microglia/potassium channel Kv1.3/inflammatory factor分类
医药卫生引用本文复制引用
陈星星,陈正薰,张蝶,江浩鹏,陶杰,汤乐乐,袁易..钾通道Kv1.3介导创伤性脑损伤后神经功能障碍及神经炎症[J].中国药理学与毒理学杂志,2025,39(6):401-411,11.基金项目
国家自然科学基金(82074162) National Natural Science Foundation of China(82074162) （82074162）
