辅酶Q10通过调节载脂蛋白E和磷酸化Tau蛋白表达对七氟醚所致幼鼠认知功能障碍的保护作用
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辅酶Q10通过调节载脂蛋白E和磷酸化Tau蛋白表达对七氟醚所致幼鼠认知功能障碍的保护作用
翻译：何幼芹 编辑：冯玉蓉 审校：曹莹
背景及目的：多次施行麻醉和手术的儿童可能更容易出现学习障碍。辅酶Q10（CoQ10）可减轻七氟醚多次给药引起的6日龄幼鼠认知功能障碍，但其具体机制尚不清楚。本研究旨在揭示载脂蛋白E(ApoE)在七氟醚麻醉所致认知障碍发病机制中的作用，以及CoQ10在七氟醚多次麻醉幼鼠模型中的保护机制。
方法：小鼠随机分为4组：对照组+玉米油、七氟醚+玉米油、对照组+CoQ10、七氟醚+CoQ10。七氟醚组小鼠用3%七氟醚加60%氧气麻醉，每天2h，连续3d，对照组小鼠只吸入60%氧气。小鼠在吸入氧气或七氟醚前30min腹腔注射CoQ10 50 mg/kg或等量玉米油，连续3d。小鼠在出生后第6~8天接受七氟醚麻醉或对照处理。实验第8天取大脑皮层和海马组织。检测ATP、MMP、ApoE mRNA、总ApoE、ApoE片段、Aβ1-40、Aβ1-42、Tau5、AT8和PHF水平。麻醉或对照处理后于P30 ~ P36进行Morris水迷宫(MWM)试验。
结果：结果表明，七氟醚麻醉前注射CoQ10可逆转麻醉引起的幼鼠活力缺乏、线粒体功能障碍、ApoE及其片段表达、Aβ1-42生成、Tau磷酸化及认知功能障碍。
结论：研究数据表明，ApoE及其片段表达增强可能在七氟醚麻醉所致认知功能障碍的发病机制中发挥重要作用。CoQ10可通过改善能量补充和线粒体功能来降低ApoE表达，从而减轻七氟醚所致的脑损伤和认知功能障碍。
原始文献来源：Yang M, Tan H, Zhang K, et al. Protective effects of Coenzyme Q10 against sevoflurane-induced cognitive impairment through regulating apolipoprotein E and phosphorylated Tau expression in young mice[J]. Int. J. Dev. Neurosci., 2020, undefined: undefined.
Protective effects of Coenzyme Q10 against sevoflurane-induced cognitive impairment through regulating apolipoprotein E and phosphorylated Tau expression in young mice
Abstract
Children with multiple exposures to anesthesia and surgery may be more likely to develop 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 4 groups: Control + corn oil, Sevoflurane + corn oil, Control + CoQ10 and Sevoflurane + CoQ10. Sevoflurane group mice were anesthetized with 3% sevoflurane and 60% oxygen 2 hours a day for 3 days, while control group mice received only 60% oxygen. Mice received intraperitoneal injection of 50mg/kg CoQ10 or the same volume of corn oil 30 min before 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, Aβ1-40, Aβ1-42, 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 reversed the anesthesia induced energy deficiency, mitochondrial dysfunction, ApoE and its fragments expression, Aβ1-42 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.
贵州医科大学高鸿教授课题组
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