硫化氢供体治疗后可限制短暂性全脑缺血期间的神经元损伤，并调节钾电压门控通道亚家族D成员2（Kv4.2）和钾通道相互作用蛋白3（KChIP3）。
Post-treatment with a Hydrogen Sulfide Donor Limits Neuronal Injury and Modulates Potassium Voltage-gated Channel Subfamily D Member 2 (Kv4.2) and Potassium Channel Interacting Protein 3 (KChIP3) During Transient Global Cerebral Ischemia.
作者信息
Bai Cheng Ping, Zhao ChenLiang, Shen Lijuan
机构信息
Department of Neurology, Affiliated Hospital of Qinghai University, 810001, Xining, Qinghai, China.
Department of Critical Care Medicine, The Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China.
出版信息
Curr Neurovasc Res. 2017;14(4):397-405. doi: 10.2174/1567202614666171108113447.
BACKGROUND
Although the neuroprotective effect of sodium hydrosulfide (NaHS, a hydrogen sulfide donor) pretreatment has been revealed, the effect of NaHS post-conditioning remains largely unknown.
OBJECTIVE
We aimed to investigate the neuroprotective effect of NaHS post-conditioning against transient Global Cerebral Ischemia (tGCI)-induced hippocampal CA1 injury and its underlying molecular mechanism.
METHODS
A tGCI rat model was established using the four-vessel occlusion method for 15 min of ischemia. The survival of hippocampal neurons was determined by Nissl staining and NeuN immunostaining. Protein expression of potassium voltage-gated channel subfamily D member 2 (Kv4.2) and potassium channel interacting protein 3 (KChIP3) was assessed by Immunohistochemistry (IHC) and Western blot.
RESULTS
Decreased concentrations (12 and 24 µmol/kg) of NaHS post-conditioning significantly increased the numbers of survival neurons and NeuN-positive neurons in the hippocampal CA1 region at 7 days post-tGCI (all P<0.05). NaHS post-conditioning (24 µmol/kg) at 12 and 24 hr posttGCI can achieve the best protective effect (both P<0.05). IHC data demonstrated that NaHS postconditioning (24 µmol/kg) markedly attenuated tGCI-induced down-regulation of Kv4.2 protein in the hippocampal CA1 region at 26 hr post-tGCI. Confocal images showed that Kv4.2 did not express in the neuronal nuclei but predominantly express in the neuronal dendrites. In addition, NaHS post-conditioning significantly up-regulated Kv4.2 and down-regulated KChIP3 in tGCI rats at 26 and 168 hr post- tGCI (all P<0.05).
CONCLUSION
Decreased concentrations of NaHS post-conditioning at 12-24 hr post-tGCI effectively protected hippocampal CA1 neurons from tGCI-induced injury, which may be through regulating the expression of Kv4.2 and KChIP3.
背景
尽管已揭示硫化氢供体硫氢化钠（NaHS）预处理具有神经保护作用，但NaHS后处理的效果在很大程度上仍不清楚。
目的
我们旨在研究NaHS后处理对短暂性全脑缺血（tGCI）诱导的海马CA1区损伤的神经保护作用及其潜在分子机制。
方法
采用四动脉闭塞法建立tGCI大鼠模型，缺血15分钟。通过尼氏染色和NeuN免疫染色确定海马神经元的存活情况。通过免疫组织化学（IHC）和蛋白质免疫印迹法评估钾电压门控通道亚家族D成员2（Kv4.2）和钾通道相互作用蛋白3（KChIP3）的蛋白表达。
结果
tGCI后7天，NaHS后处理浓度降低（12和24 μmol/kg）显著增加海马CA1区存活神经元和NeuN阳性神经元的数量（均P<0.05）。tGCI后12和24小时给予NaHS后处理（24 μmol/kg）可达到最佳保护效果（均P<0.05）。免疫组织化学数据表明，tGCI后26小时，NaHS后处理（24 μmol/kg）显著减轻了tGCI诱导的海马CA1区Kv4.2蛋白下调。共聚焦图像显示，Kv4.2不在神经元细胞核中表达，而是主要在神经元树突中表达。此外，在tGCI后26和168小时，NaHS后处理显著上调tGCI大鼠的Kv4.2并下调KChIP3（均P<0.05）。
结论
tGCI后12 - 24小时给予浓度降低的NaHS后处理可有效保护海马CA1神经元免受tGCI诱导的损伤，这可能是通过调节Kv4.2和KChIP3的表达实现的。
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