镧暴露对子代大鼠学习记忆及海马组蛋白H3K4me3表达的影响  

Effect of lanthanum exposure on learning and memory and expressing of histone H3K4me3 in hippocampus of offspring rats

作　　者：郭志新 王军 王泓颖 肖瑶 张馨心 刘慧颖 GUO Zhixin;WANG Jun;WANG Hongying;XIAO Yao;ZHANG Xinxin;LIU Huiying(不详;School of Public Health,Shenyang Medical College,Shenyang,Liaoning 110034,China)

机构地区：[1]沈阳医学院公共卫生学院,辽宁沈阳110034 [2]辽宁省军区沈阳第十四离职干部休养所门诊部 [3]辽宁省行为与认知神经科学重点实验室

出　　处：《中国工业医学杂志》2023年第5期401-404,共4页Chinese Journal of Industrial Medicine

基　　金：辽宁省“兴辽英才计划”项目(XLYC1808012);辽宁省大学生创新创业训练计划项目(20198003)。

摘　　要：目的探讨镧暴露对子代大鼠学习记忆能力及海马组蛋白H3赖氨酸4三甲基化(H3K4me3)水平的影响。方法将24只SPF级雌性Wistar孕鼠随机分为对照组,2.5、5.0和10.0 g/L氯化镧(LaCl_(3))染毒组,其子代大鼠断乳后通过自由饮水方式按原浓度继续镧暴露。而后在不同时间采用Morris水迷宫实验检测子代大鼠的学习记忆能力,ELISA法测定海马中组蛋白甲基转移酶(HMT)的活性,Western blot法检测海马中H3K4me3和脑源性神经营养因子(BDNF)的蛋白表达水平。结果与对照组比较,出生后第14、21、28、35和49天LaCl_(3)染毒组子代大鼠体质量明显下降(P<0.05)。LaCl_(3)染毒组子代大鼠寻找逃逸平台的潜伏期延长(P<0.05),穿越平台次数和目标象限停留时间均减少(P<0.05),提示子代大鼠空间学习记忆能力受损;与对照组相比,LaCl_(3)染毒组子代大鼠海马HMT活性降低(P<0.05),H3K4me3和BDNF蛋白表达水平均降低(P<0.05),并呈剂量-反应关系。结论镧暴露导致子代大鼠学习记忆能力损伤可能与海马组蛋白H3K4me3表达下降有关。Objective To investigate the effect of lanthanum exposure on learning and memory ability,and expressing of histone H3 lysine 4 trimethylation(H3K4me3)in hippocampus of offspring rats.Methods Twenty-four SPF female pregnant Wistar rats were randomly divided into control group and 2.5,5.0 and 10.0 g/L of lanthanum chloride exposed groups,the offspring rats were continuously exposed to lanthanum by free drinking water at their mothers exposed concentration after weaning.Then the Morris water maze test was used at different time point to examine the abilities of learning and memory in offspring rats.Meantime,the activity of histone methyltransferase(HMT)in hippocampus was measured using the ELISA method,the expression of histone H3K4me3 and brain-derived neurotrophic factor(BDNF)in hippocampus were determined by Western blot method.Results The results showed that compared with the control group,the body weight of the offspring rats in all the LaCl_(3)exposed groups decreased significantly(P<0.05)on the 14th,21st,28th,35th,and 49th day after birth;the escape latency in all the offsprings of LaCl_(3)exposed rats was prolonged(P<0.05),the frequency of crossing the platform and the residence time in the target quadrant were both less(P<0.05),indicating that the spatial learning and memory ability of the offspring rats were impaired;additionally,compared with the control group,the activity of HMT in hippocampus of the offspring of LaCl_(3)exposed rats were decreased(P<0.05),and the protein expression of histone H3K4me3 and BDNF were both decreased(P<0.05)in a dose-response relationship manner.Conclusion The results suggested that the impairment of learning and memory abilities in offsprings of lanthanum exposed rats may be related to the decrease of H3K4me3 expression in hippocampus.

关 键 词：氯化镧(LaCl_(3)) 组蛋白H3赖氨酸4三甲基化(H3K4me3) 组蛋白甲基转移酶(HMT) 学习记忆 子代大鼠 

分 类 号：R994[医药卫生—毒理学]