吉林大学学报(医学版)2018,Vol.44Issue(1):24-29,后插3,7.DOI:10.13481/j.1671-587x.20180105
异氟醚对缺锌APP/PS1转基因阿尔茨海默病模型小鼠海马神经元凋亡的影响
Effect of isoflurane anesthesia on hippocampus neuroapoptosis in zinc-deficient APP/PS1 transgenic mice of Alzheimer's disease models
摘要
Abstract
Objective:To study the effect of isoflurane anesthesia on the hippocampal neuroapoptosis in the zincdeficient APP/PS1 transgenic mice,and to clarify its related mechanisms.Methods:The eight-month or ninemonth old APP/PS1 transgenic mice were randomly assigned to four groups (n=24):zinc adequate (ZA) group,the mice were given a standard diet for 2 months;zinc adequate+ isoflurane (ZA+ Iso) group,the mice were given a standard diet for 2 months then exposed to 1.4% isoflurane for 2 h;zinc-deficient (ZD) group,the mice were given zinc deficient diet for 1 month;zinc deficient with isoflurane (ZD+Iso) group,the mice were given zinc deficient diet for 1 month and then exposed to 1.4% isoflurane for 2 h.The hippocampus tissue of the mice were obtained 24 h after anesthesia.The immunofluorescence double staining was performed to measure the apoptotic rates of hippocampal neurons.The Western blotting method was used to detect the expression levels of Aβ and Cleaved caspase-3 and the ratio of Bax/Bcl-2.Results:Compared with ZA group,the apoptotic rate of neurons,the ratio of Bax/Bcl-2 and the expression level of Cleaved caspase-3 of the mice in ZA+Iso group were increased 6 h after isoflurane exposure (P<0.05 or P<0.01);but no differences were found in the apoptotic rate of neurons and the expression levels of total Aβ,Aβ40 and Aβ42 24 h after isoflurane exposure (P>0.05).Compared with ZA group,the apoptotic rates of neurons,the ratios of Bax/Bcl-2,the expression levels of Aβ42 and Cleaved caspase-3 of the mice in ZD group and ZD+ Iso group were increased 6 and 24 h after isoflurane exposure (P<0.05or P<0.01).Compared with ZD group,the apoptotic rate of neurons,the expression levels of Aβ42,Bax/Bcl-2and Cleaved caspase-3 and the ratio of Bax/Bcl-2 of the mice in ZD+Iso group were elevated significantly 6 and 24 h after isoflurane exposure (P<0.05 or P<0.01).Conclusion:1.4% isoflurane exposure for 2 h can induce the transient elevation of hippocampal neuroapoptosis in the ten-month old APP/PS1 transgenic mice.1.4 % isoflurane exposure for 2 h can significantly aggravate the hippocampal neuroapoptosis in the zinc-deficient APP/PS1 transgenic mice,it is probably associated with the hippocampal Aβ aggregation,activation of Bax and Caspase-3 and inhibition of Bcl-2.关键词
缺锌/异氟醚/阿尔茨海默病/β淀粉样蛋白/神经元凋亡Key words
zinc deficiency/isoflurane/Alzheimer's disease/amyloid β-peptide/neuron apoptosis分类
医药卫生引用本文复制引用
冯安琪,刘楠,朴美花,苑野,裴爱月,刘娅,冯春生..异氟醚对缺锌APP/PS1转基因阿尔茨海默病模型小鼠海马神经元凋亡的影响[J].吉林大学学报(医学版),2018,44(1):24-29,后插3,7.基金项目
国家自然科学基金资助课题(81141065,81271215) (81141065,81271215)
吉林省科技厅科技发展计划项目资助课题(20150101170JC) (20150101170JC)
中国博士后科学基金资助课题(2016M591489) (2016M591489)