Abstract: Objective: To study the effect of isoflurane anesthesia on the hippocampal neuroapoptosis in the zinc-deficient APP/PS1 transgenic mice,and to clarify its related mechanisms. Methods: The eight-month or nine-month 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<0.05 or P<0.01).Compared with ZD group,the apoptotic rate of neurons,the expression levels of Aβ42,Bax/Bcl-2 and 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.

Key words: zinc deficiency, neuron apoptosis, Alzheimer's disease, amyloid β-peptide, isoflurane