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DNA甲基转移酶在苯并[a]芘致小鼠空间学习记忆功能障碍中的改变 [中文引用][英文引用]

The Change of DNA Methyltransferase in Mice with Spatial Learning and Memory Impairment Induced by Benzo[a]pyrene

作者(英文):CAO Jingjing  HAO Zhongsuo  LIU Aixiang  LI Huan  ZHANG Zhihong  ZHANG Hongmei 
单位:山西医科大学 
单位(英文): 
分类号:R114
出版年·卷·期(页码):2018·8·第1期(1-6)
DOI:
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目的 研究DNA甲基转移酶在苯并[a]芘(B[a]P)致小鼠学习记忆功能障碍中的改变,为B[a]P神经毒作用机制的研究提供科学依据。方法 将48只成年雄性SPF级hauschka(ICR)小鼠按体重随机分为4组,每组12只,分别为溶剂(花生油)对照组,0.5 mg/kg(低剂量)、2.0 mg/kg(中剂量),和10.0 mg/kg(高剂量)B[a]P染毒组,隔天腹腔注射染毒1次,连续染毒30次。染毒结束后,用Morris水迷宫检测小鼠的空间学习记忆能力。并在染毒第10、20和30次后,用实时荧光定量-聚合酶链式反应(qPCR)和酶联免疫吸附试验(ELISA)检测小鼠大脑皮质DNA甲基转移酶(DNMTs)的基因表达和蛋白活性的改变。结果 水迷宫结果显示,随着染毒剂量的增加,小鼠到达平台的潜伏期逐渐延长,高剂量组潜伏期显著高于溶剂对照组,差异有统计学意义(P<0.05);小鼠进入目标象限的总次数和在目标象限的游泳路程逐渐减少,高剂量组显著低于溶剂对照组,差异有统计学意义(P<0.05);与溶剂对照组相比,各染毒组小鼠大脑皮质中DNA甲基转移酶DNMT1、DNMT3a和DNMT3b的基因表达量和蛋白激酶的活性均逐渐增强,呈明显的剂量和时间依赖性,差异有统计学意义(P<0.05)。结论 B[a]P诱导大脑皮质DNA甲基转移酶DNMT1、DNMT3a和DNMT3b基因表达水平和蛋白激酶的活性增强,可能是B[a]P致小鼠空间学习记忆障碍的重要机制之一。

-----英文摘要:---------------------------------------------------------------------------------------

Objectives To investigate the change of DNA methyltransferase (DNMT) mRNA levels and their kinase activities in ICR mice with learning and memory impairment induced by benzo[a]pyrene(B[a]P). Methods Forty-eight adult male ICR mice were categorized randomly into 4 groups based on body weight, one solvent control group and three B[a]P-treated groups at the dosage of 0.5 mg/kg (low-dose), 2 mg/kg (mid-dose) and 10 mg/kg (high-dose). B[a]P-treated mice were intra-peritoneally injected with B[a]P once every two days for 30 times of administration. At the end of 30th administration, Morris water maze test was used to determine the spatial learning and memory ability of mice. The change of DNMT1, DNMT3a and DNMT3b mRNA levels were detected by using a real-time fluorescence quantitative-polymerase chain reaction (qPCR), and the DNMT1, DNMT3a and DNMT3b kinase activity were determined by using an enzyme linked immunosorbent assay (ELISA) at the end of 10th, 20th and 30th administration. Results Morris water maze test showed an increase of average escape latency time with the dose of B[a]P injected in mice, the escape latency time was significantly longer in the high-dose group than that in the solvent control group (P<0.05). The frequency of crossing platform and the swimming distance in the target quadrant were gradually decreased with the dose of B[a]Ps, which were both significantly increased in the high-dose group as compared to the solvent control group (P<0.05). Compared with the solvent control group, DNMT1, DNMT3a and DNMT3b mRNA levels and their kinase activities were significantly increased in cerebral cortex in B[a]P-treated groups (P<0.05), and were significantly dependent on the duration and the dose of B[a]P administration (P<0.05). Conclusions B[a]P administration could result in the increase of DNMT1, DNMT3a and DNMT3b mRNA levels and their kinase activities in cerebral cortex in mice, which might be the potential critical mechanism of learning and memory deficits induced by B[a]P.

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中文著录格式: 曹晶晶,,郝忠锁,,刘爱香,,李欢,,张志红,,张红梅.DNA甲基转移酶在苯并[a]芘致小鼠空间学习记忆功能障碍中的改变.环境卫生学杂志.2018;8(1):1-6.
英文著录格式: CAO,Jingjing,,HAO,Zhongsuo,,LIU,Aixiang,,LI,Huan,,ZHANG,Zhihong,,ZHANG,Hongmei.The Change of DNA Methyltransferase in Mice with Spatial Learning and Memory Impairment Induced by Benzo[a]pyrene..2018;8(1):1-6.

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