Neuroprotection of Sevoflurane Against Ischemia/Reperfusion-Induced Brain Injury Through Inhibiting JNK3/Caspase-3 by Enhancing Akt Signaling Pathway
Neuroprotection of Sevoflurane Against Ischemia/Reperfusion-Induced Brain Injury Through Inhibiting JNK3/Caspase-3 by Enhancing Akt Signaling Pathway
复制标题
七氟醚通过增强 Akt 信号通路抑制 JNK3/Caspase-3 对缺血/再灌注引起的脑损伤的神经保护作用
DOI：
10.1007/s12035-015-9111-8
复制
发表时间：
2016-04-01
影响因子：
5.1
通讯作者：
Song, Yuan-Jian
中科院分区：
文献类型：
--
作者：
Wen, Xiang-Ru;Fu, Yan-Yan;Song, Yuan-Jian
在这项研究中，我们研究了七氟醚对缺血性脑损伤的神经保护作用及其潜在的分子机制。四支血管闭塞致成年雄性Sprague-Dawley大鼠短暂性脑缺血。缺血前分别用七氟醚或七氟醚联合LY294002/wortmannin （PI3K选择性抑制剂）预处理大鼠。甲酚紫染色检测海马CA1锥体神经元的存活情况。采用免疫印迹法和免疫沉淀法检测Akt1、PRAS40、ASK1和JNK3的磷酸化水平和cleaved-caspase-3的表达。结果表明，吸入2%七氟醚2小时对缺血/再灌注诱导的海马神经元死亡具有显著的神经保护作用。七氟醚显著提高了Akt和PRAS40的磷酸化水平，并在再灌注后6小时降低了ASK1的磷酸化水平，在再灌注后15分钟后3天降低了JNK3的磷酸化水平。LY294002和wortmannin则明显抑制七氟醚的作用。综上所述，七氟醚可能通过增加缺血/再灌注时Akt1的磷酸化，下调ASK1/JNK3级联的激活，从而抑制缺血性脑损伤。
In this study, we investigated the neuroprotective effect of sevoflurane against ischemic brain injury and its underlying molecular mechanisms. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The rats were pretreated with sevoflurane alone or sevoflurane combined with LY294002/wortmannin (selective inhibitor of PI3K) before ischemia. Cresyl violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. Immunoblotting and immunoprecipitation were performed to measure the phosphorylation of Akt1, PRAS40, ASK1, and JNK3 and the expression of cleaved-caspase-3. The results demonstrated that a moderate dose of sevoflurane inhalation of 2 % for 2 h had significant neuroprotective effects against ischemia/reperfusion induced hippocampal neuron death. Sevoflurane significantly increased Akt and PRAS40 phosphorylation and decreased the phosphorylation of ASK1 at 6 h after reperfusion and the phosphorylation of JNK3 at 3 days after reperfusion following 15 min of transient global brain ischemia. Conversely, LY294002 and wortmannin significantly inhibited the effects of sevoflurane. Taken together, the results suggest that sevoflurane could suppress ischemic brain injury by downregulating the activation of the ASK1/JNK3 cascade via increasing the phosphorylation of Akt1 during ischemia/reperfusion.