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The potential dual effects of sevoflurane on AKT/GSK3β signaling pathway

机译：七氟醚对AKT /GSK3β信号通路的潜在双重影响

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Background Anesthesia with multiple exposures of commonly used inhalation anesthetic sevoflurane induces neuroinflammation and cognitive impairment in young mice, but anesthesia with a single exposure to sevoflurane does not. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway is involved in neurotoxicity and neurobehavioral deficits. However, whether sevoflurane can induce a dual effect (increase versus decrease) on the activation of AKT/GSK3β signaling pathway remains to be determined. We therefore set out to assess the effects of sevoflurane on AKT/GSK3β signaling pathway in vivo and in vitro. Methods Six day-old wild-type mice were exposed to 3% sevoflurane two hours daily for one or three days. In the in vitro studies, H4 human neuroglioma cells were treated with 4% sevoflurane for two or six hours. We then determined the effects of different sevoflurane treatments on the levels of phosphorylated (P)-GSK3β(ser9) and P-AKT(ser473) by using Western blot analysis. Results Here we show that anesthesia with 3% sevoflurane two hours daily for one day increased the levels of P-GSK3β(ser9) and P-AKT(ser473), but the anesthesia with 3% sevoflurane daily for three days decreased them in the mice. The treatment with 4% sevoflurane for two hours increased, but the treatment with 4% sevoflurane for six hours decreased, the levels of P-GSK3β(ser9) and P-AKT(ser473) in the H4 human neuroglioma cells. Conclusions Anesthetic sevoflurane might induce a dual effect (increase versus decrease) on the activation of the AKT/GSK3β signaling pathway. These studies have established a system to perform further studies to determine the effects of sevoflurane on brain function.
机译：背景多次吸入常用麻醉麻醉剂七氟醚引起的麻醉在幼年小鼠中引起神经炎症和认知障碍，但一次接触七氟醚引起的麻醉则不会。 AKT /糖原合酶激酶3β（GSK3β）信号传导途径与神经毒性和神经行为缺陷有关。然而，七氟醚是否可以对AKT /GSK3β信号通路的激活产生双重作用（增加还是减少）尚待确定。因此，我们着手评估体内和体外七氟醚对AKT /GSK3β信号通路的影响。方法六天大的野生型小鼠每天2小时暴露于3％的七氟醚中，持续1或3天。在体外研究中，用4％七氟醚处理H4人神经胶质瘤细胞2到6个小时。然后，我们通过Western blot分析确定了不同的七氟醚处理对磷酸化（P）-GSK3β（ser9）和P-AKT（ser473）水平的影响。结果在这里我们显示，每天2小时使用3％七氟醚的麻醉持续1天会增加P-GSK3β（ser9）和P-AKT（ser473）的水平，但是每天3％的七氟醚的麻醉持续3天会使小鼠的P-GSK3β（ser9）和P-AKT（ser473）的水平降低。用4％七氟醚治疗2小时增加，但是用4％七氟醚治疗6小时减少，H4人神经胶质瘤细胞中P-GSK3β（ser9）和P-AKT（ser473）的水平。结论麻醉药七氟醚可能对AKT /GSK3β信号通路的激活具有双重作用（增加与减少）。这些研究建立了进行进一步研究以确定七氟醚对脑功能的影响的系统。

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