异氟醚对转APP基因小鼠脑内海马神经元蛋白质损伤和蛋白聚集的影响

doi:10.13481/j.1671-587x.20160406

吉林大学学报(医学版) ›› 2016, Vol. 42 ›› Issue (04): 665-670.doi: 10.13481/j.1671-587x.20160406

异氟醚对转APP基因小鼠脑内海马神经元蛋白质损伤和蛋白聚集的影响

刘楠¹, 冯春生¹, 朴美花¹, 刘明², 孙宇田³

1. 吉林大学第一医院麻醉科, 吉林长春 130021;
2. 吉林省前卫医院神经外科, 吉林长春 130012;
3. 吉林大学中日联谊医院药学部, 吉林长春 130033

收稿日期:2015-11-30 发布日期:2016-07-20
通讯作者: 孙宇田,主管药师(Tel:0431-84995836,E-mail:happybo126@126.com) E-mail:happybo126@126.com
作者简介:刘楠(1987-),女,吉林省长春市人,医师,医学硕士,主要从事临床麻醉药物对阿尔茨海默病发病机制影响方面的研究。
基金资助:
国家自然科学基金资助课题（81271215，81141065）；吉林省科技厅科技发展计划项目资助课题（20150101170JC）

Influence of isoflurane in neuronal protein damage and aggregation in APP transgenic mouse hippocampus

LIU Nan¹, FENG Chunsheng¹, PIAO Meihua¹, LIU Ming², SUN Yutian³

1. Department of Anesthesiology, First Hospital, Jilin University, Changchun 130021, China;
2. Department of Neurosurgery, Qianwei Hospital, Jilin Province, Changchun 130012, China;
3. Department of Pharmacy, China-Japan Union Hospital, Jilin University, Changchun 130033, China

Received:2015-11-30 Published:2016-07-20

摘要/Abstract

摘要：

目的：观察吸入麻醉药异氟醚对转APP基因小鼠脑内海马神经元蛋白质损伤和蛋白聚集的影响，并探讨海藻糖对异氟醚诱导的神经毒性的干预作用。方法：60只12月龄转APP基因小鼠随机分为对照组、异氟醚组（Iso组）和海藻糖组（Tre组），每组20只。对照组小鼠不给予任何药物，将其置于持续通入2 L·min^-1氧气的麻醉箱中2h；Iso组和Tre组小鼠于麻醉前30 min分别经腹腔注射2 mL生理盐水或海藻糖（400 μg·kg^-1）稀释液，然后给予1.4%异氟醚吸入麻醉2 h。麻醉后6 h 取小鼠海马组织制备脑组织匀浆，应用 DCFH-DA荧光法检测小鼠海马组织中活性氧（ROS）水平；麻醉后24 h应用免疫组织化学法和Western blotting法检测小鼠海马组织中蛋白羰基化合物、硝基化酪氨酸和β-淀粉样蛋白（Aβ）_1-42蛋白表达水平，应用透射电镜检测海马神经元中蛋白聚集物的形成，应用TUNEL染色法观察小鼠海马组织中神经元凋亡率。结果：与对照组比较，Iso组小鼠海马组织中ROS水平、氧化蛋白羰基化合物、硝基化酪氨酸、Aβ_1-42蛋白表达水平和神经元凋亡率均明显增加（P < 0.05）；与Iso组比较，Tre组小鼠海马组织中ROS水平、氧化蛋白羰基化合物、硝基化酪氨酸、Aβ_1-42蛋白表达水平和神经元凋亡率均明显降低（P < 0.05）。结论：异氟醚能诱导转APP基因小鼠海马神经元蛋白质损伤和蛋白聚集，加剧氧化应激反应，增加脑内海马神经元凋亡，海藻糖能够拮抗异氟醚诱导的神经毒性。

关键词: 异氟醚, 阿尔茨海默病, 蛋白质损伤, 细胞凋亡, 海藻糖

Abstract:

Objective: To observe the influence of inhaled anesthetic isoflurane in the neuronal protein damage and aggregation in the APP transgenic mouse hippocampus, and to investigate the intervention effect of trehalose. Methods: Sixty APP transgenic mice aged 12 months were divided into control group,isoflurane group (Iso group) and trehalose group (Tre group)(n=20). The rats in control group were not given any drugs and were put into the anesthetic box with continuonsly entering 2 L·min^-1 oxygen for 2 h;the rats in Iso group and Tre group were respectively injected intraperitoneally with 2 mL saline or trehalose (400 μg·kg^-1) 30 min before anesthesia,and then inhalated 1.4% isoflurane for 2 h. 6 h after anesthesia,the hippocampus tissue of the mice was prepared,and DCFH-DA fluorescence was applied to detect the reactive oxygen species (ROS) level;24 h after anesthesia,immunohistochemical method and Western blotting method were used to detect the contents of carbonyl compounds and nitrotyrosine and the Aβ_1-42 protein expression level in hippocampus;TEM was applied to observe the formation of protein aggregates;TUNEL staining was performed to observe the apoptotic rate of hippocampal neurons. Results: Compared with control group,the ROS level,the expression levels of oxidative protein carbonyl compounds and nitrotyrosine, the expression level of Aβ_1-42 protein,and the apoptotic rate of hippocampal neurons in Iso group were significantly increased (P< 0.05);compared with Iso group,the ROS level,the expression levels of oxidative protein carbonyl compounds and nitrotyrosine, the Aβ_1-42 protein expression level,and the apoptotic rate of hippocampal neurons in Tre group were significantly decreased (P < 0.05). Conclusion: Isoflurane can induce the protein damage and aggregation,the apoptotic rate of hippocampal neurons,aggravate oxidative stress reaction,increase the apoptotic rate of brain hippocampal neurons in the APP transgenic mice;trehalose can intervene the neurotoxicity induced by inhaled anesthetics.

Key words: isoflurane, Alzheimer's disease, protein damage, apoptosis, trehalose

中图分类号:

R742

刘楠, 冯春生, 朴美花, 刘明, 孙宇田. 异氟醚对转APP基因小鼠脑内海马神经元蛋白质损伤和蛋白聚集的影响[J]. 吉林大学学报(医学版), 2016, 42(04): 665-670.

LIU Nan, FENG Chunsheng, PIAO Meihua, LIU Ming, SUN Yutian. Influence of isoflurane in neuronal protein damage and aggregation in APP transgenic mouse hippocampus[J]. Journal of Jilin University Medicine Edition, 2016, 42(04): 665-670.

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异氟醚对转APP基因小鼠脑内海马神经元蛋白质损伤和蛋白聚集的影响

Influence of isoflurane in neuronal protein damage and aggregation in APP transgenic mouse hippocampus

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