Effect of zinc deficiency factor on cognitive function after isoflurane anesthesia in mice with Alzheimer's disease / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of zinc deficiency factor on cognitive function after isoflurane anesthesia in mice with Alzheimer's disease (AD).Methods One hundred and forty-four APP/ PS1 transgenic mice with AD,weighing 22-28 g,aged 8-10 months,were divided into 6 groups (n=24 each) using a random number tablezinc adequate group (group ZA),zinc adequate plus isoflurane anesthesia group (group ZA+Iso),zinc deficiency group (group ZD),zinc deficiency plus isoflurane anesthesia group (group ZD+Iso),zinc treatment group (group ZT) and zinc treatment plus isoflurane anesthesia group (group ZT+Iso).The mice were fed a diet adequate in zinc and deionized water for 2 months in ZA and ZA+Iso groups.The mice were fed a diet low in zinc (0.01‰ zinc) and deionized water for 1 month in ZD and ZD+Iso groups.The mice were fed a diet adequate in zinc and 0.12‰ ZnSO4 · 7H2O water for 2 months in ZT and ZT+Iso groups.The mice underwent 2 h of anesthesia with 1.4％ isoflurane starting from the end of feeding in ZA+Iso,ZD+Iso and ZT+Iso groups.At 24 h after anesthesia,the mice were sacrificed and hippocampal tissues were obtained for determination of the contents of soluble amyloid beta protein 40 (Aβ40) and Aβ42 and insoluble Aβ40 and Aβ42 (using enzyme-linked immunosorbent assay) and expression of total Aβ,Aβ40,Aβ42,tau pSer396,tau pSer262 and tau pThr231 (by Western blot).Morris water maze test was performed at 24 h after anesthesia.Results There was no significant difference in each parameter between group ZA and group ZA+Iso and between group ZT and group ZT+Iso (P＞0.05).Compared with group ZD or group ZT+Iso,the escape latency was significantly prolonged,the space exploration time was shortened,the expression of hippocampal Aβ42,tau pSer396,tau pSer262 and tau pThr231 was up-regulated,and the contents of soluble and insoluble Aβ42 were increased in group ZD+Iso (P＜0.05 or 0.01).Conclusion Zinc deficiency can aggravate the impairment of cognitive function after isoflurane anesthesia in mice with AD,and the mechanism is related to the promotion of hippocampal Aβ aggregation and tau protein phosphorylation.