Objective: Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia-reperfusion (IR) injury, but the underlying mechanisms have not been fully elucidated. Besides, different protocols would usually lead to different results. The objective of this study was to determine whether dual exposure to sevoflurane improves the effect of anesthetic preconditioning against oxygen and glucose deprivation (OGD) injury in vitro.
Methods: Rat hippocampal slices under normoxic conditions (95% O2/5% CO2) were pre-exposed to sevoflurane 1, 2 and 3 minimum alveolar concentration (MAC) for 30 min, once or twice, with 15-min washout after each exposure. The slices were then subjected to 13-min OGD treatment (95% N2/5% CO2, glucose-free), followed by 30-min reoxygenation. The population spikes (PSs) were recorded in the CA1 region of rat hippocampus. The percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment was calculated, since it could indicate the recovery degree of neuronal function. In addition, to assess the role of mitogen-activated protein kinases (MAPKs) in preconditioning, U0126, an inhibitor of extracellular signal-regulated protein kinase (MEK-ERK1/2, ERK1/2 MAPK), and SB203580, an inhibitor of p38 MAPK, were separately added 10 min before sevoflurane exposure.
Results: Preconditioning once with sevoflurane 1, 2, and 3 MAC increased the percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment, from (15.13+/-3.79)% (control) to (31.88+/-5.36)%, (44.00+/-5.01)%, and (49.50+/-6.25)%, respectively, and twice preconditioning with sevoflurane 1, 2, and 3 MAC increased the percentage to (38.53+/-4.36)%, (50.74+/-7.05)% and (55.86+/-6.23)%, respectively. The effect of duplicate preconditioning with sevoflurane 3 MAC was blocked by U0126 [(16.23+/-4.62)%].
Conclusion: Sevoflurane preconditioning can induce neuroprotection against OGD injury in vitro, and preconditioning twice enhances this effect. Besides, the activation of extracellular signal-regulated protein kinase (MEK-ERK1/2, ERK1/2 MAPK) may be involved in this process.
目的: 大量研究表明, 吸入麻醉药预处理可以降低脑缺血再灌注损伤, 但吸入预处理的机制还不甚清楚, 不同的给药方案可能会产生不同的效果。 本研究旨在探讨七氟醚重复预处理是否能增强单次预处理对缺氧无糖 (oxygen and glucose deprivation, OGD) 损伤大脑的保护作用及其可能的机制。
方法: 大鼠海马脑片经最低肺泡有效浓度 (minimum alveolar concentration, MAC) 为1、 2 和 3 的七氟醚单次或双次预处理 (每次持续30 min), 每次预处理后冲洗15 min, 然后进行 13 min OGD 损伤, 再复氧供糖30 min。 在这些过程中记录 CA1 区群峰电位 (population spikes, PSs), 损伤后PS 的恢复程度代表神经功能的恢复程度。 为研究丝裂原活化蛋白激酶 (mitogen-activated protein kinases, MAPKs) 在七氟醚预处理中的作用, 在七氟醚预处理前 10 min 加入细胞外信号调节蛋白激酶 (extracellular signal-regulated protein kinase, MEK-ERK1/2) 抑制剂 U0126 和 p38 MAPK抑制剂 SB203580。
结果: 1 MAC、 2 MAC 和 3 MAC 七氟醚单次预处理后, 神经功能的恢复程度分别为 (31.88±5.36)%、 (44.00±5.01)% 和 (49.50±6.25)%, 对照组为 (15.13±3.79)%; 1 MAC、 2 MAC和 3 MAC 七氟醚双次预处理后, 神经功能的恢复程度分别为 (38.53±4.36)%、 (50.74±7.05)% 和 (55.86±6.23)%。 此外, U0126 能抑制 3 MAC 七氟醚双次预处理的保护作用 [(18.5±5.23)% vs (55.86±6.23)%]。
结论: 以上结果提示, 七氟醚预处理具有神经保护作用, 且七氟醚重复预处理诱导的神经保护作用强于单次预处理的神经保护作用。 此外, MEK-ERK1/2 的活化参与了七氟醚预处理对 OGD 损伤大脑的保护作用。