Protective effects of Coenzyme Q10 against sevoflurane-induced cognitive impairment through regulating apolipoprotein E and phosphorylated Tau expression in young mice
Protective effects of Coenzyme Q10 against sevoflurane-induced cognitive impairment through regulating apolipoprotein E and phosphorylated Tau expression in young mice
复制标题
辅酶Q10通过调节载脂蛋白E和磷酸化Tau的表达对七氟醚致幼鼠认知功能障碍的保护作用
DOI：
10.1002/jdn.10041
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发表时间：
2020-08-01
影响因子：
1.8
通讯作者：
Yu, Yonghao
中科院分区：
文献类型：
--
作者：
Yang, Man;Tan, Hong;Yu, Yonghao
多次接受麻醉和手术的儿童可能更容易出现学习障碍。据报道，辅酶 Q10 (CoQ10) 可减少 6 日龄幼鼠多重七氟醚治疗引起的认知缺陷。但其具体机制尚未被发现。本研究旨在揭示ApoE在七氟烷麻醉引起的认知缺陷发病机制中的作用以及辅酶Q10在七氟烷多重治疗幼鼠模型中的保护机制。将小鼠随机分为四组：对照+玉米油、七氟烷+玉米油、对照+CoQ10和七氟烷+CoQ10。七氟醚组小鼠用 3% 七氟醚和 60% 氧气麻醉，每天 2 小时，持续 3 天，而对照组小鼠仅接受 60% 氧气。小鼠在吸氧或七氟醚前30 min腹腔注射50 mg/kg CoQ10或等体积玉米油，连续3天。小鼠在出生后第6至第8天接受七氟醚麻醉或对照治疗。第8天收获皮层和海马。检测ATP、MMP、ApoE mRNA、总ApoE、ApoE片段、Aβ1-40、Aβ1-42、Tau5、AT8和PHF水平。在麻醉或对照治疗后从 P30 到 p36 进行莫里斯水迷宫 (MWM) 测试。结果表明，在七氟醚治疗前注射CoQ10可以逆转幼年小鼠因麻醉引起的能量缺乏、线粒体功能障碍、ApoE及其片段表达、Aβ1-42生成、Tau磷酸化和认知障碍。这些数据提示ApoE及其片段的增强可能在七氟烷麻醉引起的认知缺陷的发病机制中发挥重要作用。 CoQ10可以通过改善能量补充和线粒体功能来减少ApoE表达，从而减轻七氟烷引起的脑损伤和认知障碍。
Children with multiple exposures to anesthesia and surgery may be more likely to develop the learning disability. Coenzyme Q10 (CoQ10) was reported to reduce the multiple sevoflurane treatment-induced cognitive deficiency in 6-day-old young mice. However, its specific mechanisms have not yet been found. This research aimed to reveal the role of ApoE in the pathogenesis of cognitive deficiency caused by sevoflurane anesthesia and the protective mechanism of CoQ10 in a multiple sevoflurane treatment model of young mice. The mice were randomly divided into four groups: Control + corn oil, Sevoflurane + corn oil, Control + CoQ10, and Sevoflurane + CoQ10. Sevoflurane group mice were anesthetized with 3% sevoflurane and 60% oxygen 2 hr a day for 3 days, while control group mice received only 60% oxygen. Mice received an intraperitoneal injection of 50 mg/kg CoQ10 or the same volume of corn oil 30 min before the inhalation of oxygen or sevoflurane for 3 days. Mice received sevoflurane anesthesia or control treatment from the 6th to 8th day after birth. The cortex and hippocampus were harvested on the 8th day. The ATP, MMP, ApoE mRNA, total ApoE, ApoE fragments, A beta 1-40, A beta 1-42, Tau5, AT8, and PHF levels were detected. The Morris water maze (MWM) tests were performed from P30 to p36 after anesthesia or control treatment. The results indicated that the injection of CoQ10 ahead of sevoflurane treatment could reverse the anesthesia-induced energy deficiency, mitochondrial dysfunction, ApoE, and its fragments expression, A beta 1-42 generation, Tau phosphorylation, and cognitive impairment in young mice. These data reveal that the ApoE and its fragments enhancement may play an important role in the pathogenesis of cognitive deficiency caused by sevoflurane anesthesia. CoQ10 could reduce ApoE expression by improving energy replenishment and mitochondrial functions, thereby alleviating sevoflurane-induced brain damage and cognitive impairment.