Sevoflurane pre- and post-conditioning protect the brain via the mitochondrial KATP channel
Sevoflurane pre- and post-conditioning protect the brain via the mitochondrial KATP channel
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DOI：
10.1093/bja/aep365
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发表时间：
2010-02-01
影响因子：
9.8
通讯作者：
Lebuffe, G.
中科院分区：
文献类型：
--
作者：
Adamczyk, S.;Robin, E.;Lebuffe, G.
本研究旨在评价在大鼠局灶性脑缺血模型中，在再灌注开始时暴露于七氟烷是否提供类似于七氟烷预处理的保护作用，以及该作用是否依赖于线粒体钾ATP依赖性通道（mitoK（ATP））。预处理包括在缺血前72小时以1个最低肺泡浓度（2.6%）暴露于七氟烷15分钟。通过在再灌注开始时立即暴露于七氟烷或在再灌注开始后5 min延迟暴露进行后处理。通过在每次七氟烷给药前腹腔注射选择性阻断剂5-羟基癸酸酯或通过给予mitoK（ATP）通道开放剂二氮嗪（DZX）代替七氟烷，评估mitoK（ATP）通道的作用。再灌注后24 h和7 d评价脑梗死面积、神经功能缺损评分和运动协调性。七氟醚预处理和早期后处理降低了再灌注24 h时的脑梗死面积和神经功能缺损评分，而单独的七氟醚后处理改善了运动协调性。在第7天，只有梗死体积保持较低的预处理和后处理的动物。七氟烷介导的神经保护作用在再灌注开始后5分钟时丧失，并通过抑制mitoK（ATP）而消除。DZX单独模拟七氟醚诱导的预处理和后处理。在局灶性脑缺血大鼠模型中，七氟醚预处理或再灌注早期给药可通过mitoK（ATP）提供神经保护作用。
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.