Department of Surgery, Second Hospital, Jilin University, Changchun, Jilin 130041, P.R. China.
Mol Med Rep. 2014 Mar;9(3):843-50. doi: 10.3892/mmr.2014.1912. Epub 2014 Jan 22.
Obesity is associated with increased infarct volumes and adverse outcomes following ischemic stroke. However, its effect on anesthetic postconditioning‑induced neuroprotection has not been investigated. The present study examined the effect of sevoflurane postconditioning on focal ischemic brain injury in diet‑induced obesity. Sprague‑Dawley rats were fed a high‑fat diet (HF; 45% kcal as fat) for 12 weeks to develop obesity syndrome. Rats fed a low‑fat diet (LF; 10% kcal as fat) served as controls. The HF or LF‑fed rats were subjected to focal cerebral ischemia for 60 min, followed by 24 h of reperfusion. Postconditioning was performed by exposure to sevoflurane for 15 min immediately at the onset of reperfusion. The involvement of the mitochondrial KATP (mitoKATP) channel was analyzed by the administration of a selective inhibitor of 5‑hydroxydecanoate (5‑HD) prior to sevoflurane postconditioning or by administration of diazoxide (DZX), a mitoKATP channel opener, instead of sevoflurane. The cerebral infarct volume, neurological score and motor coordination were evaluated 24 h after reperfusion. The HF‑fed rats had larger infarct volumes, and lower neurological scores than the LF‑fed rats and also failed to respond to neuroprotection by sevoflurane or DZX. By contrast, sevoflurane and DZX reduced the infarct volumes and improved the neurological scores and motor coordination in the LF‑fed rats. Pretreatment with 5‑HD inhibited sevoflurane‑induced neuroprotection in the LF‑fed rats, whereas it had no effect in the HF‑fed rats. Molecular studies demonstrated that the expression of Kir6.2, a significant mitoKATP channel component, was reduced in the brains of the HF‑fed rats compared with the LF‑fed rats. The results of this study indicate that diet‑induced obesity eliminates the ability of anesthetic sevoflurane postconditioning to protect the brain against cerebral ischemic neuronal injury, most likely due to an impaired brain mitoKATP channel.
肥胖与缺血性中风后的梗死体积增加和不良预后有关。然而，其对麻醉后处理诱导的神经保护作用尚未得到研究。本研究探讨了七氟醚后处理对饮食诱导肥胖所致局灶性缺血性脑损伤的影响。Sprague-Dawley 大鼠给予高脂肪饮食（HF；45%热量来自脂肪）喂养 12 周以建立肥胖综合征。给予低脂肪饮食（LF；10%热量来自脂肪）的大鼠作为对照。HF 或 LF 喂养的大鼠进行 60 min 的局灶性脑缺血，随后进行 24 h 的再灌注。后处理通过在再灌注开始时立即暴露于七氟醚 15 min 来进行。通过在七氟醚后处理之前给予 5-羟基癸酸（5-HD）的选择性抑制剂或给予线粒体 KATP（mitoKATP）通道开放剂二氮嗪（DZX）来分析线粒体 KATP（mitoKATP）通道的参与。再灌注 24 h 后评估脑梗死体积、神经评分和运动协调。HF 喂养的大鼠的梗死体积较大，神经评分较低，并且未能对七氟醚或 DZX 的神经保护作用产生反应。相比之下，七氟醚和 DZX 降低了 LF 喂养的大鼠的梗死体积，改善了其神经评分和运动协调。5-HD 的预处理抑制了 LF 喂养的大鼠中七氟醚诱导的神经保护作用，但对 HF 喂养的大鼠没有影响。分子研究表明，与 LF 喂养的大鼠相比，HF 喂养的大鼠大脑中 Kir6.2 的表达，一个重要的 mitoKATP 通道组成部分减少。这项研究的结果表明，饮食诱导的肥胖消除了麻醉后处理七氟醚保护大脑免受缺血性神经元损伤的能力，这很可能是由于大脑 mitoKATP 通道受损所致。
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