目的:研究强效真核细胞翻译起始因子2α(eIF-2α)激酶抑制剂2-氨基嘌呤(2-AP)对载脂蛋白E缺陷(apoE^-/-)小鼠肝功能、肝组织形态和动脉粥样硬化(AS)的影响。方法:肝脏功能、形态研究:将apoE^-/-小鼠随机分为3组,即对照组、200mg/Kg和300mg/Kg 2-AP两药物干预组,30天内每两天用2-AP灌胃一次,分析各组血浆谷丙转氨酶(ALT)和谷草转氨酶(AST)水平、肝组织形态和肝脏重量(干重、湿重、干重/湿重比、湿重/体重比)变化。AS研究:将apoE^-/-小鼠随机分为对照组和200mg/Kg 2-AP干预组,后者84天内每两天灌胃一次2-AP。观测两组AS病变面积、血浆总胆固醇(TC)和甘油三酯(TG)含量。结果:200、300mg/Kg 2-AP组apoE^-/-小鼠血浆ALT、AST、肝脏重量各指标、肝组织形态与空白对照组比较差异均无统计学意义(P〉0.05)。200mg/Kg 2-AP组apoE^-/-小鼠AS病变面积明显小于对照组,差异有统计学意义(P〈0.05);血浆TC、TG水平与对照组比较,差异无统计学意义(P〉0.05)。结论:实验剂量2-AP不影响apoE^-/-小鼠肝脏组织形态及功能,其防治AS作用不依赖降低血脂水平。
Objective:To study the effect of 2-Aminopurine(2-AP)on apolipoprotein E knockout(apoE^-/-)mice and observe the change of liver morphology,function and the development of atherosclerosis(AS).Method:ApoE^-/-mice were divided into 3groups:control group,200mg/Kg and 300mg/Kg BW 2-AP group.2-AP treated groups were fed with 2-AP by gavage once every for 30days.Then plasma alanine transaminase(ALT),aspartate aminotransferase(AST)level,liver morphology,liver weight(dry,wet,dry/wet,wet/body weight)were analyzed.For AS study,mice were divided into 2groups:control group and 2-AP treated group,2-AP treated group were fed with 2-AP(200mg/Kg)by gavage once every for 84days,the area of atherosclerotic plaque,plasma cholesterol(TG)and triglyceride(TG)levels of two groups were detected.Results:Compared with the control apoE^-/-mice,2-AP treated mice did not show significant changes in liver weight,liver morphology,ALT and AST.Furthermore,treatment with 200mg 2-AP/Kg BW for 84days significantly reduced the area of atherosclerotic plaque,but did not alter plasma TC and TG levels.Conclusion:Oral feeding of 2-AP at the experimental doses will not affect the mice's liver morphology and function,the reduce of the area of atherosclerotic plaque does not depend on blood lipid.