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

作　　者：冯安琪 刘楠[1] 朴美花[1] 苑野[1] 裴爱月[2] 刘娅[3] 冯春生[1] 

机构地区：[1]吉林大学第一医院麻醉科,吉林长春130021 [2]吉林大学第一医院内镜中心,吉林长春130021 [3]吉林大学公共卫生学院营养与食品卫生学教研室,吉林长春130021

出　　处：《吉林大学学报（医学版）》2018年第1期24-29,共6页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(81141065;81271215);吉林省科技厅科技发展计划项目资助课题(20150101170JC);中国博士后科学基金资助课题(2016M591489)

摘　　要：目的:研究吸入麻醉药异氟醚对缺锌APP/PS1转基因小鼠海马神经元凋亡的影响,探讨其相关作用机制。方法:8和9月龄APP/PS1转基因小鼠随机分为常锌组、常锌+异氟醚组、缺锌组和缺锌+异氟醚组,每组24只。常锌组小鼠给予正常锌含量饮食2个月;常锌+异氟醚组小鼠给予正常锌含量饮食2个月后接受1.4%异氟醚麻醉2h;缺锌组小鼠给予低锌饮食1个月;缺锌+异氟醚组小鼠给予低锌饮食1个月后接受1.4%异氟醚麻醉2h。分别在麻醉后6和24h杀鼠取海马组织,采用免疫荧光双染法检测海马神经元凋亡率,Western blotting法检测海马β淀粉样蛋白(Aβ)、活化型半胱氨酸天门冬氨酸特异性蛋白酶3(Cleaved caspase-3)表达水平和Bax/Bcl-2比值。结果:与常锌组比较,常锌+异氟醚组小鼠麻醉后6h海马神经元凋亡率、Cleaved caspase-3表达水平和Bax/Bcl-2比值升高(P<0.05或P<0.01),麻醉后24h海马神经元凋亡率总Aβ、Aβ40和Aβ42表达水平无明显改变(P>0.05);缺锌组和缺锌+异氟醚组小鼠麻醉后6和24h海马神经元凋亡率、Aβ42表达水平、Cleaved caspase-3表达水平和Bax/Bcl-2比值升高(P<0.05或P<0.01)。与缺锌组比较,缺锌+异氟醚组小鼠麻醉后6和24h海马神经元凋亡率、Aβ42和Cleaved caspase-3表达水平及Bax/Bcl-2比值进一步升高(P<0.05或P<0.01)。结论:10月龄常锌APP/PS1转基因小鼠给予1.4%异氟醚麻醉2h能够短暂加重其海马神经元凋亡;1.4%异氟醚麻醉2h能够明显加重缺锌APP/PS1转基因小鼠海马神经元凋亡,其作用机制可能与促进海马Aβ42聚集、增强Bax表达、抑制Bcl-2表达和激活Caspase-3有关。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 hafter 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 Aβand 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 hafter 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 hafter 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 hcan induce the transient elevation of hippocampal neuroapoptosis in the ten-month old APP/PS1 transgenic mice.1.4%isoflurane exposure fo

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 

分 类 号：R743[医药卫生—神经病学与精神病学]