Influence of isoflurane in neuronal protein damage and aggregation in APP transgenic mouse hippocampus / 吉林大学学报(医学版)

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.