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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Aβ1-40、Aβ1-42、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Aβ1-40、Aβ1-42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Aβ1-40、Aβ1-42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Aβ1-40、Aβ1-42的含量,抑制Aβ相关基因AβPP的表达,上调Nep蛋白的表达。
Objective To investigate the effects of EGCG on learning and memory impairment of hippocampus in young rats exposed to lead during lactation and its effect on beta amyloid and neprilysin. Methods SPF grade C57BL / 6 pregnant rats were randomly divided into control group and lead exposure group. Pregnant rats in lead exposed group drank 0.5% lead acetate solution in lactation period and control group received distilled water. After the lead exposure, 40 male offspring of lead-exposed male rats (divided into low, medium and high doses of EGCG intervention group and lead exposure model group, 10 rats in each group), 10 male offspring of control group were treated with different concentration EGCG solution and saline were intragastrically administered for 21 days. Morris water maze test was used to detect the learning and memory ability of mice in each group. The content of lead in blood was determined by graphite furnace atomic absorption spectrometry and the levels of Aβ1-40 , Aβ1-42, AβPP mRNA, AβPP, neprilysin (Nep) were measured. Results Compared with control group, the levels of blood lead in low, medium and high dose EGCG intervention groups were significantly lower than those in control group (P <0.001). There was no significant difference in blood lead levels between EGCG intervention group and lead exposure model group (P = 0.174,0.086,0.071). The escape latency of lead exposure model group was higher than that of control group (P <0.001), and the escape latency of medium and high dose EGCG intervention group was lower than that of lead exposure model group (P <0.001) The content of Aβ1-40 and Aβ1-42 in the hippocampus of the model group was significantly higher than that of the control group (P <0.001), and the content of Nep in the exposed model group was significantly lower (P <0.001) 40, the content of Aβ1-42 was significantly lower than that of the model group of lead exposure, and the content of Nep was significantly increased (P <0.001). The effect of high dose EGCG intervention group was the best. Conclusion EGCG can significantly improve the learning and memory abilities of mice, and EGCG can reduce the levels of Aβ1-40 and Aβ1-42, inhibit the expression of Aβ-related gene AβPP and up-regulate the expression of Nep in mice hippocampus.