Li Luyao, Li Shan, Hu Chuanbing, Zhou Li, Zhang Yujiao, Wang Mingyan, Qi Zhi
a Department of Basic Medical Sciences , School of Medicine, Xiamen University , Xiamen , China.
b School of Psychology , Xinxiang Medical University , Xinxiang City , Henan , China.
Mol Membr Biol. 2019 Dec;35(1):9-20. doi: 10.1080/09687688.2019.1608378.
Epidemiological studies have demonstrated that vitamin C decreases the risk of stroke, which has generally been ascribed to its function as antioxidant and free radical scavenger. However, whether there is a defined molecular target for vitamin C on stroke is unknown. Utilizing middle cerebral artery occlusion (MCAO) in rats as a model for ischemic stroke, we demonstrated that long-term, low-dose administration of vitamin C prior to MCAO could exert significant neuroprotective effect on the brain damage. The long-term, low-dose vitamin C pretreated rats had decreased brain infarct size and decreased neurological deficit score compared with the vehicle or single high dose pretreated MCAO rats. Furthermore, electrophysiological experiments using patch clamp technique showed that vitamin C increased the whole-cell current of the large-conductance Ca-activated K (BK) channel. Moreover, vitamin C increased the open probability of the channel without change its amplitude. Importantly, blockade of the BK channels abolished the neuroprotective effect of vitamin C on MCAO. Therefore, this study shows that long-term, low-dose pretreatment with vitamin C could reduce MCAO-induced brain damage through activation of the BK channels, suggesting that the BK channel is a molecular target of vitamin C on stroke.
流行病学研究表明，维生素C可降低中风风险，这通常归因于其抗氧化剂和自由基清除剂的功能。然而，维生素C在中风方面是否存在明确的分子靶点尚不清楚。利用大鼠大脑中动脉闭塞（MCAO）作为缺血性中风模型，我们证明在MCAO之前长期、低剂量给予维生素C可对脑损伤发挥显著的神经保护作用。与溶剂或单次高剂量预处理的MCAO大鼠相比，长期、低剂量维生素C预处理的大鼠脑梗死面积减小，神经功能缺损评分降低。此外，使用膜片钳技术进行的电生理实验表明，维生素C增加了大电导钙激活钾（BK）通道的全细胞电流。此外，维生素C增加了通道的开放概率，而不改变其幅度。重要的是，阻断BK通道消除了维生素C对MCAO的神经保护作用。因此，本研究表明，长期、低剂量维生素C预处理可通过激活BK通道减少MCAO诱导的脑损伤，提示BK通道是维生素C在中风方面的分子靶点。
