摘要：
目的 探讨青、少年期低脂饮食或他汀干预对中年期Tg2576小鼠行为学及脑内β-淀粉样蛋白(Aβ)病理的影响. 方法 将35只2月龄Tg2576小鼠按随机数字表法分为少年低脂组、少年他汀组、青年低脂组、青年他汀组及空白对照组,每组7只.其中低脂组采用标准低脂饲料喂养,他汀组采用阿托伐他汀钙片[17 mg/(kg· d)]加入至普通饲料中喂养,少年组、青年组的干预月龄分别设置为2月龄、6月龄,空白对照组给予常规喂养.所有小鼠饲养至10月龄统一处死,处死前2周内采用Moms水迷宫实验进行行为学测试,处死后取外周血测定血脂生化水平,取大脑行免疫病理染色测定脑组织切片中组织淀粉样蛋白免疫活性(TAPIR)及行ELISA法检测脑组织匀浆中Aβ40、Aβ42、β-分泌酶、γ-分泌酶浓度. 结果 与空白对照组比较,各干预组小鼠的逃避潜伏期、穿越隐蔽平台次数、TAPIR强阳性比例及Aβ40、γ-分泌酶浓度差异均无统计学意义(P＞0.05),且青年低脂组、青年他汀组的Aβ42浓度及青年他汀组的β-分泌酶浓度均明显高于空白对照组,差异均有统计学意义(P＜0.05). 结论 青、少年期低脂饮食或他汀干预并不能改善中年期Tg2576小鼠的行为学及脑内Aβ病理,反而有潜在加速阿尔茨海默病进程的风险.%Objective To investigate the effects of low-fat diet or statin intervention at early age on brain amyloid β-protein (Aβ) pathology and behaviors of middle-aged Tg2576 mice.Methods Thirty-five two-month-old Tg2576 mice were randomly divided into following 5 groups:a juvenile statin group,a juvenile low-fat diet group,a young statin group,a young low-fat group,and a blank control group (n=7);mice in the low-fat diet groups were given standard low-fat feed,and mice in the statin group were given atorvastatin at 17 mg/(kg· d) into the normal diet.The initiation times of intervention were,respectively,set to be 2-month-old in juvenile groups and 6-month-old in young groups;meanwhile,mice in the blank-control group were fed with normal diet without statin.All mice were raised to be 10-month-old and tested by Morris water maze for evaluating cognitive behaviors two weeks before execution.After peripheral blood and brains being taken,a monoclonal anti-Aβ42 antibody was employed to immunostain mice brain paraffin tissue sections for assaying tissue Aβ plaque immunoreactivity (TAPIR),and the levels of Aβ40,Aβ42,β-secretase,and γ-secretase in homogenates were detected by enzyme-linked immunosorbent assays (ELISA).Results As compared with those in the blank-control group,the average escape latencies,times of passing through hidden platforms,percentage of strong TAPIR,Aβ42 and γ-secretase level in all intervention groups showed no statistical differences (P＞0.05).As compared with those in the blank control group,Aβ42 in homogenates of young intervention groups and β-secretase level in the young statin group were significantly higher (P＜0.05).Conclusion Interventions initiated from juvenile or young,and low-fat diet intervention or statin intervention can neither improve the mice's Morris water maze testing results,nor reduce Aβs burdens in brain homogenates and Aβ40 immunopathologies in brain tissues of middle-aged mice;over early initiation of low-fat diet intervention or statin intervention might accelerate or worsen Alzheimer's disease progress.
