EGCG对铅暴露C57BL/6仔鼠海马Aβ蛋白及NEP酶表达的影响

doi:10.6040/j.issn.1671-7554.0.2015.1231

山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (12): 8-13.doi: 10.6040/j.issn.1671-7554.0.2015.1231

EGCG对铅暴露C57BL/6仔鼠海马Aβ蛋白及NEP酶表达的影响

尹延彦^1,2,赵林远^1,3,张晓欢¹,黄辉¹,孙贝贝¹,李文杰¹

1.郑州大学公共卫生学院营养与食品卫生教研室, 河南郑州 450001;2.新乡医学院基础医学院, 河南新乡 453003;3.漯河市医专第一附属医院营养科, 河南漯河 462000

收稿日期:2015-12-02 出版日期:2016-12-10 发布日期:2016-12-10
通讯作者: 李文杰. E-mail:lwj@zzu.ed E-mail:lwj@zzu.ed
基金资助:
国家自然科学基金(81172716)

Effects of EGCG on the expressions of hippocampal amyloid beta protein and neprilysin enzyme in C57BL/6 young mice exposed to lead

YIN Yanyan^1,2, ZHAO Linyuan^1,3, ZHANG Xiaohuan¹, HUANG Hui¹, SUN Beibei¹, LI Wenjie¹

1. College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China;
2. College of Basic Medicine, Xinxiang Medical University, Xinxiang 453003, Henan, China;
3.Department of Clinical Nutrition, The first Afficiated Hospital, Luohe Medical College, Luohe 462000 Henan, China

Received:2015-12-02 Online:2016-12-10 Published:2016-12-10

摘要/Abstract

摘要： 目的探讨不同剂量的表没食子儿茶素没食子酸酯(EGCG)对哺乳期铅暴露仔鼠海马学习记忆能力损伤的作用,及对β淀粉样蛋白、脑啡肽酶的影响。方法选取SPF级C57BL/6孕鼠,随机分为对照组和铅暴露组。铅暴露组孕鼠在哺乳期饮用0.5%醋酸铅水溶液,对照组饮用蒸馏水。染铅结束后,取40只染铅雄性仔鼠(分为低、中、高剂量EGCG干预组、铅暴露模型组,每组各10只),对照组10只雄性仔鼠,分别用不同浓度的EGCG溶液和生理盐水等体积灌胃21 d,采用Morris水迷宫实验检测各组小鼠学习记忆能力,石墨炉原子吸收光谱法测定各组小鼠血铅含量,并对海马组织中Aβ_1-40、Aβ_1-42、AβPP mRNA、AβPP、脑啡肽酶( Nep)的蛋白含量进行测定。结果铅暴露模型组,低、中、高剂量EGCG干预组的血铅含量明显高于对照组(P<0.001),低、中、高剂量EGCG干预组和铅暴露模型组血铅含量比较差异无统计学意义(P=0.174,0.086,0.071);铅暴露模型组逃避潜伏期高于对照组(P<0.001),中、高剂量EGCG干预组的逃避潜伏期低于铅暴露模型组(P<0.001);铅暴露模型组小鼠海马内Aβ_1-40、Aβ_1-42的含量与对照组比较明显升高(P<0.001),Nep含量明显降低(P<0.001),中、高剂量EGCG干预组Aβ_1-40、Aβ_1-42的含量与铅暴露模型组比较明显降低,Nep含量明显升高(P<0.001),其中以高剂量EGCG干预组效果最佳。结论 EGCG干预能明显提高小鼠的学习记忆能力,且EGCG能够降低小鼠海马组织中Aβ_1-40、Aβ_1-42的含量,抑制Aβ相关基因AβPP的表达,上调Nep蛋白的表达。

关键词: β淀粉样前体蛋白, β_1-40淀粉样蛋白, 表没食子儿茶素没食子酸酯, β_1-42淀粉样蛋白, 脑啡肽酶, 生命早期铅暴露

Abstract: Objective To explore the effects of different doses of epigallocatechin 3 gallate, table gallic catechin gallic acid ester(EGCG)on the learning and memory ability, amyloid beta and neprilysin enzymes in lactation mice which were exposed to lead. Methods SPF pregnant C57BL/6 mice were divided into control group(drank distilled water, n=4)and lead exposure group(drank 0.5% Pb-contaminated acetic acid solution, n=14). Another 40 male lead-exposed mice were divided into 4 groups, low EGCG group(1.5 mg/kg), which are moderate EGCG group(3.0 mg/kg), 山东大学学报 (医学版)54卷12期 -尹延彦,等.EGCG对铅暴露C57BL/6仔鼠海马Aβ蛋白及NEP酶表达的影响 \=-high EGCG group(4.5 mg/kg)and lead exposure group, with 10 mice in each group. Another 10 male mice served as the control group(normal saline). After 21 days of treatment, all rats’ learning and memory ability was tested with Morris water maze experiment; the lead content in blood and hippocampus was determined with graphite furnace atomic absorption spectrometer; the protein contents of Aβ_1-40, Aβ_1-42, AβPP mRNA, AβPP and the neprilysin enzyme were also detected. Results The lead exposure group, and low, moderate and high EGCG groups had significantly higher content of blood lead than the control group(P<0.05). There was no difference among EGCG groups and lead exposure group(P=0.174, 0.086, 0.071). Lead exposure group had longer escaping latency than the control group(P<0.001), while the EGCG group had shorter escaping latency than the control group(P<0.001). Compared with the control group, the lead exposure group had increased content of Aβ_1-40 and Aβ_1-42(P<0.001), and decreased Nep content(P<0.001); the moderate and high EGCG groups had decreased Aβ_1-40 and Aβ_1-42 content and increased Nep content(P<0.001), and the high EGCG group had better interventional effect. Conclusion EGCG intervention can significantly improve the learning and memory ability of mice. EGCG can reduce Aβ_1-40 and Aβ_1-42 contents in the hippocampus, inhibit the expression of related gene AβPP, and upregulate the Nep protein expression.

Key words: Lead exposure in early life, Beta-amyloid precursor protein, Aβ_1-40, Neprilysin, Epigallocatechin-3-gallate, Aβ_1-42

中图分类号:

R135.1+1

尹延彦,赵林远,张晓欢,黄辉,孙贝贝,李文杰. EGCG对铅暴露C57BL/6仔鼠海马Aβ蛋白及NEP酶表达的影响[J]. 山东大学学报（医学版）, 2016, 54(12): 8-13.

YIN Yanyan, ZHAO Linyuan, ZHANG Xiaohuan, HUANG Hui, SUN Beibei, LI Wenjie. Effects of EGCG on the expressions of hippocampal amyloid beta protein and neprilysin enzyme in C57BL/6 young mice exposed to lead[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(12): 8-13.

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EGCG对铅暴露C57BL/6仔鼠海马Aβ蛋白及NEP酶表达的影响

Effects of EGCG on the expressions of hippocampal amyloid beta protein and neprilysin enzyme in C57BL/6 young mice exposed to lead

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