Effect of isoflurane anesthesia on hippocampus neuroapoptosis in zinc-deficient APP/PS1 transgenic mice of Alzheimer's disease models / 吉林大学学报(医学版)

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.