海藻糖对异氟烷诱导转APP基因小鼠海马氧化应激损伤的影响

发布时间：2018-11-27 15:21

【摘要】：目的探讨吸入麻醉药异氟烷对转APP基因小鼠海马氧化应激损伤的影响及海藻糖的可能保护作用机制。方法随机将12月龄转APP小鼠分为四组(n=15):正常对照组(Control组)、异氟烷组(Iso组)、异氟烷+海藻糖组(Iso+Tre组)、海藻糖组(Tre组)。正常对照组,小鼠不做任何处理;Iso组,小鼠给予1.4%异氟烷麻醉2 h;Iso+Tre组,小鼠于麻醉前30 min腹腔注射海藻糖400μg/kg,然后给予1.4%异氟烷麻醉2 h;Tre组,小鼠腹腔注射海藻糖400μg/kg处理。部分小鼠麻醉后24 h应用Morris水迷宫检测学习记忆能力。部分小鼠在麻醉后6 h杀鼠取双侧海马组织,一侧海马制备脑组织匀浆,应用二氯二氢荧光素-乙酰乙酸酯(DCFH-DA)荧光法检测活性氧(ROS)水平,化学发光法测定丙二醛(MDA)含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性;另一侧海马制作脑组织切片,应用TUNEL染色观察小鼠海马神经元凋亡,免疫组织化学法检测海马SOD、GSH-Px、CAT的表达。结果与正常对照组比较,Iso组小鼠逃避潜伏期明显延长(P0.05),空间探索时间明显缩短(P0.05),海马ROS水平明显增高(P0.05),MDA含量明显增高(P0.05),SOD、GSH-Px、CAT活性明显降低(P0.05),海马神经元凋亡率明显增加(P0.05);与Iso组相比较,Iso+Tre组小鼠逃避潜伏期明显缩短(P0.05),空间探索时间明显延长(P0.05),海马ROS水平明显降低(P0.05),MDA含量明显降低(P0.05),SOD、GSH-Px、CAT活性明显升高(P0.05),海马神经元凋亡率明显减少(P0.05)。结论吸入麻醉药异氟烷能够诱导转APP基因小鼠学习记忆能力损害,加剧海马氧化应激损伤,海藻糖能够通过抗氧化作用来拮抗异氟烷的神经毒性。
[Abstract]:Objective to investigate the effects of inhaled anesthetic isoflurane on oxidative stress in hippocampus of APP transgenic mice and the possible protective mechanism of trehalose. Methods 12-month-old APP mice were randomly divided into four groups: normal control group (Control group), isoflurane group (Iso group), isoflurane trehalose group (Iso Tre group) and trehalose group (Tre group). In Iso group, mice were anesthetized with 1.4% isoflurane for 2 h. The mice were given intraperitoneal injection of trehalose 400 渭 g / kg 30 min before anesthesia, then 1.4% isoflurane for 2 h. In Tre group, mice were treated with trehalose 400 渭 g/kg intraperitoneally. Morris water maze was used to test the learning and memory ability of some mice 24 hours after anesthesia. Some mice were killed 6 hours after anesthesia to take bilateral hippocampal tissues and one side of hippocampus to prepare brain homogenate. The level of reactive oxygen species (ROS) was detected by DCFH-DA fluorescence method. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD),) glutathione peroxidase (GSH-Px) and catalase (CAT) (CAT) were determined by chemiluminescence. TUNEL staining was used to observe the apoptosis of hippocampal neurons and the expression of SOD,GSH-Px,CAT in hippocampus was detected by immunohistochemical method. Results compared with the normal control group, the escape latency in Iso group was significantly prolonged (P0.05), the spatial exploration time was shortened (P0.05), and the level of ROS in hippocampus was significantly increased (P0.05), SOD,). The activity of GSH-Px,CAT decreased significantly (P0.05), and the apoptosis rate of hippocampal neurons increased significantly (P0.05). Compared with Iso group, the escape latency of mice in, Iso Tre group was significantly shortened (P0.05), the time of spatial exploration was prolonged (P0.05), and the level of ROS in hippocampus was significantly decreased (P0.05), MDA content, P0.05, SOD,GSH-Px,). The activity of CAT increased significantly (P0.05), and the apoptosis rate of hippocampal neurons decreased significantly (P0.05). Conclusion inhaled anesthetic isoflurane can induce learning and memory impairment in mice with APP gene and aggravate oxidative stress injury in hippocampus. Trehalose can antagonize neurotoxicity of isoflurane through antioxidation.
【作者单位】：吉林大学第一医院麻醉科;
【基金】：国家自然科学基金资助课题(81141065,81271215)
【分类号】：R614

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