Department of Pharmacology, Lille 2 University Medical School, France.
Br J Anaesth. 2010 Feb;104(2):191-200. doi: 10.1093/bja/aep365.
This study aimed to evaluate whether exposure to sevoflurane at the onset of reperfusion provides protection similar to sevoflurane preconditioning and whether the effect depends on mitochondrial potassium ATP-dependent channel (mitoK(ATP)) in a rat model of focal cerebral ischaemia.
Adult Wistar male rats were subjected to focal cerebral ischaemia for 1 h followed by 24 h or 7 days of reperfusion. Preconditioning consisted of 15 min exposure to sevoflurane at 1 minimum alveolar concentration (2.6%) 72 h before ischaemia. Post-conditioning was performed by exposure to sevoflurane immediately at the onset of reperfusion or by a delayed exposure 5 min after the onset of reperfusion. The role of the mitoK(ATP) channel was assessed by i.p. injection of the selective blocker 5-hydroxydecanoate before each sevoflurane administration or by the mitoK(ATP) channel opener, diazoxide (DZX), given in place of sevoflurane. Cerebral infarct size, neurological deficit score, and motor coordination were evaluated 24 h and 7 days after reperfusion.
Sevoflurane preconditioning and early post-conditioning reduced both cerebral infarct size and neurological defect score at 24 h of reperfusion whereas the sole sevoflurane post-conditioning improved motor coordination. At 7 days, only infarct volume remained lower in pre- and post-conditioned animals. Neuroprotection mediated by sevoflurane was lost when it was given 5 min after the onset of reperfusion and was abolished by inhibition of mitoK(ATP). DZX alone mimicked sevoflurane-induced pre- and post-conditioning.
The pretreatment with sevoflurane or its early administration at reperfusion provides neuroprotection via mitoK(ATP) in a rat model of focal cerebral ischaemia.
本研究旨在评估在再灌注起始时暴露于七氟醚是否提供类似于七氟醚预处理的保护作用，以及该效应是否取决于大鼠局灶性脑缺血模型中的线粒体钾 ATP 依赖性通道（mitoK(ATP)）。
成年 Wistar 雄性大鼠接受 1 小时局灶性脑缺血，随后进行 24 小时或 7 天的再灌注。预处理包括在缺血前 72 小时暴露于七氟醚 1 个最小肺泡浓度（2.6%）15 分钟。后处理是在再灌注开始时立即暴露于七氟醚，或在再灌注开始后 5 分钟延迟暴露。通过在每次七氟醚给药前腹腔注射选择性阻滞剂 5-羟癸酸或用线粒体 KATP 通道开放剂二氮嗪（DZX）代替七氟醚来评估 mitoK(ATP) 通道的作用。再灌注后 24 小时和 7 天时评估脑梗死体积、神经功能缺损评分和运动协调能力。
七氟醚预处理和早期后处理均能降低再灌注 24 小时后的脑梗死体积和神经功能缺损评分，而单独的七氟醚后处理则能改善运动协调能力。在 7 天时，只有预处理和后处理动物的梗死体积仍较低。当七氟醚在再灌注开始后 5 分钟给予时，其介导的神经保护作用丧失，而 mitoK(ATP) 抑制则消除了这种作用。DZX 单独给药可模拟七氟醚诱导的预处理和后处理。
在大鼠局灶性脑缺血模型中，七氟醚预处理或再灌注早期给药通过 mitoK(ATP) 提供神经保护作用。
