Journal of Jilin University Medicine Edition ›› 2016, Vol. 42 ›› Issue (04): 665-670.doi: 10.13481/j.1671-587x.20160406

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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. 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

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 Aβ1-42 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 Aβ1-42 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 Aβ1-42 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

CLC Number: 

  • R742