铝致大鼠认知能力和全基因组甲基化改变的研究  

Research of aluminum to the cognitive ability and genome-wide methylation in rats

作　　者：原宇宙 杨晓娟[2] 任佩[1] 亢盼 李朝阳[1] 牛侨[1] 

机构地区：[1]山西医科大学公共卫生学院,太原030001 [2]山西医科大学第一临床医学院老年病科

出　　处：《卫生研究》2015年第3期359-363,共5页Journal of Hygiene Research

基　　金：国家自然科学基金(No.81372968)

摘　　要：目的研究铝对大鼠认知能力及全基因组甲基化的影响。方法健康清洁级SD雄性大鼠72只,按体质量随机分成两部分9组,实验部分:对照组(生理盐水),低、中、高铝剂量组(0.27、0.54和1.08 mg/kg);干预部分:对照组(生理盐水),铝高剂量组(1.08 mg/kg),铝高剂量+叶酸低、中、高剂量组(0.7、1.5和3.4 mg/kg),每组8只。各组大鼠腹腔注射相应剂量麦芽酚铝(0.2 ml/d),同时叶酸各剂量干预组每日灌胃叶酸1 ml/100 g,连续60 d。采用Morris水迷宫测定大鼠学习记忆能力,采用ELISA法测定大鼠全基因组甲基化。结果 Morris水迷宫结果显示,铝暴露可导致大鼠目标象限停留时间明显缩短,穿越原平台位置的次数明显减少,铝低、中、高剂量组与对照组比较差异有统计学意义(P<0.05);叶酸干预铝高剂量组可导致大鼠目标象限停留时间明显延长和穿越原平台位置的次数明显增多,铝高剂量组与铝高+叶酸中、高剂量组比较差异有统计学意义(P<0.05)。大鼠全基因组甲基化测定结果显示:随铝染毒剂量的增加,0.54、1.08 mg/kg染毒组大鼠全基因组甲基化率显著降低,与对照组比较差异具有统计学意义(P<0.05);而添加高剂量叶酸组全基因组甲基化率显著增加,与铝高剂量组比较差异具有统计学意义(P<0.05),与对照组比较差异无统计学意义。结论铝可导致大鼠学习记忆能力下降,大鼠全基因组甲基化率降低,叶酸可能对其有改善作用。Objective To investigate the effects of aluminum exposure on cognition ability and genome-wide methylation in rats. Methods Seventy-two healthy SD male rats were randomly assigned by weight into two parts and nine groups （eight rats/group）. Exposure part included control group and low,medium and high dose aluminum maholate group （0.27,0.54 and 1.08 mg/kg alumium maholate）. Intervention part included control group, 1.08 mg/kg aluminum maltolate group, 1.08 mg/kg aluminum maholate and low,medium and high dose folic acid group （0.7,1.5 and 3.4 mg/kg folic acid）. Aluminum maholate were subjected to peritoneal injection （0.2 ml/d） and folic acid were subjected to intragastric administration in 1 ml/100 g for 60 days. The learning and memory abilities were examined by using Morris water maze test and genome-wide methylation was determined via ELISA assay. Results It was revealed by Morris water maze test that target quadrant residence time and through the original position were markedly shortened as a result of medium and high dose aluminum exposure when compared with control group （ both P 〈 0. 05 ）. The target quadrant residence time and through the original position were extended as a result of folic acid intervention when compared with 1.08 mg/kg aluminum maholate exposure group. Both of them had statistical difference between 1.08mg/kg aluminum maltolate and （1.5 mg/kg and 3.4 mg/kg） folic acid intervention group and 1.08 mg/kg aluminum maltolate exposure group （both P 〈 0.05 ）. Considerable decrease in genome-wide methylation rate was associated with elevated dosage of aluminum maltolate （0. 54 mg/kg and 1.08 mg/kg）as compared with control group （both P 〈 0.05 ）. The genome-wide methylation rate was gradually increase as a result of high-dose folic acid intervention when compared with high-dose aluminum maltolate exposure group（ both P 〈0. 05）. Both of them had nostatistical difference when compared with control group （both P 〉 0. 05 ）. Conclusion Aluminum may

关 键 词：铝 大鼠 认知能力 全基因组甲基化 

分 类 号：R994.6[医药卫生—毒理学] Q593.2[医药卫生—药学]