同型半胱氨酸对大鼠学习记忆及海马APP代谢影响  

Influence of hyperhomocysteinemia on learning and memory ability and expression of β-amyloid precursor protein of hippocampus and intervention effect of folic acid in rats

作　　者：王健[1] 张永泽[1] 康美玉[1] 潘丽兰[1] 史玉[1] 高玉梅[1] 李凤铭[1] 

机构地区：[1]河北工程大学医学院,河北邯郸056029

出　　处：《中国公共卫生》2012年第7期948-950,共3页Chinese Journal of Public Health

摘　　要：目的探讨高同型半胱氨酸血症(HHcy)对大鼠学习记忆能力和海马β-淀粉样前体蛋白(APP)代谢影响及叶酸干预作用。方法将40只Wistar大鼠随机分为对照组、HHcy组和叶酸干预组,每组10只,在大鼠饮水中添加蛋氨酸(1.0 g/kg)制作HHcy模型,叶酸低、高剂量干预组大鼠同时分别给予叶酸0.7和3.4 mg/kg灌胃,持续8周。在实验前后测定各组血浆同型半胱氨酸(Hcy)、叶酸浓度,采用Morris水迷宫试验检查大鼠学习记忆能力,观察大鼠海马区APP表达水平。结果与对照组比较,HHcy组逃避潜伏期[(29.34±4.69)s]延长,穿过平台次数[(1.36±0.98)次]减少,停留时间[(1.36±0.98)s]缩短,差异均有统计学意义(P<0.05);与HHcy组比较,高剂量叶酸组学习记忆能力明显改善;与对照组比较,HHcy组γ-分泌酶PS1基因的在mRNA表达水平(1.43±0.10)明显升高(P<0.01),与HHcy组比较,叶酸干预组明显降低;与对照组比较,HHcy组皮质和海马Aβ水平明显升高,与HHcy组比较,叶酸干预组皮质和海马Aβ水平明显降低,差异有统计学意义(P<0.05)。结论 Hh-cy可导致大鼠学习记忆能力下降,大鼠海马APP蛋白代谢改变和Aβ产生增多,叶酸对HHcy具有拮抗作用。Objective To explore the influence of hyperhomocysteinemia（HHcy） on learning and memory ability and expression of β-amyloid precursor protein of hippocampus and the intervention effect of folic acid（FA） in rats.Methods Forty Wistar rats were randomly divided into normal control group,HHcy group,and two FA intervention groups（low and high dose）.Methionine（1 g/kg · d） was dissolved in drinking water to make HHcy model.Treatment with FA（0.7 and 3.4 mg/kg · d） via intragastric intubation was administered in FA groups for 8 weeks.Plasma concentrations of homocysteinemia（Hcy） and FA before and after the experiment were measured.The rats＇ learning and memory abilities were tested by Morris water maze test.At the end of 8 weeks experiment,immunohistochemistry was used to observe the expression of β-arnyloid precusor protein（APP） in hippocampus.Results Compared with the normal control and FA groups,the escape latency in HHcy group was significantly longer;the numbers of passing the platform region was significantly less;the staying time in the platform region was significantly shorter（P0.05-0.01）;and the mean values of APP and its metabolic secretase in region of hippocampus was significantly higher（P 0.01）.The results of all tests were not significantly different between the normal control group and FA groups.Conclusion HHcy can induce learning and memory impairment and decreased the expression of APP in hippocampus in rats.FA supplementation could attenuate the adverse effects.

关 键 词：高同型半胱氨酸血症 叶酸 学习记忆能力 海马 Β-淀粉样前体蛋白 

分 类 号：R114[医药卫生—卫生毒理学]