• 关键词：邻苯二甲酸二丁酯(DBP)  阿尔茨海默病(AD)  氧化应激  学习记忆能力  海马组织

• 基金项目：湖北省教育厅科学技术研究计划指导性项目（No.B2018178）；湖北科技学院博士启动基金项目（No.2018-20XB017）；湖北省大学生创新训练计划项目（No.201810927039）

• 孙燕玲
• 湖北科技学院基础医学研究中心, 环境-免疫与神经系统疾病实验室, 咸宁 437100

• 郭荣洁
• 湖北科技学院五官医学院, 咸宁 437100

• 陈雅琦
• 湖北科技学院五官医学院, 咸宁 437100

• 杨艳芳
• 湖北科技学院五官医学院, 咸宁 437100

• 任沛瑶
• 湖北科技学院临床医学院&附属第二医院, 咸宁 437100

• 武阳
• 湖北科技学院基础医学研究中心, 环境-免疫与神经系统疾病实验室, 咸宁 437100

• 马萍
• 湖北科技学院基础医学研究中心, 环境-免疫与神经系统疾病实验室, 咸宁 437100

• 吴红年
• 湖北科技学院基础医学研究中心, 环境-免疫与神经系统疾病实验室, 咸宁 437100

• 吕建国
• 湖北科技学院临床医学院&附属第二医院, 咸宁 437100

• 摘要：为探究邻苯二甲酸二丁酯（DBP）影响阿尔茨海默病（AD）大鼠学习记忆能力的分子机制，将56只SPF级5~6周龄雌性Wistar大鼠随机平均分为7组：阴性对照组、0.25 mg·kg^-1·d^-1 DBP组、2.5 mg·kg^-1·d^-1 DBP组、25 mg·kg^-1·d^-1 DBP组、250 mg·kg^-1·d^-1 DBP组、AD模型组和AD+25 mg·kg^-1·d^-1 DBP组.连续灌胃处理28 d，观察Morris水迷宫结果，检测脑海马组织中活性氧（ROS）、还原型谷胱甘肽（GSH）、丙二醛（MDA）、8-羟基脱氧鸟苷（8-OHdG）的含量；采用实时荧光定量PCR （qPCR）检测Bcl-2、Bax和Caspase-3 mRNA的转录水平；通过免疫印迹试验（Western blot）检测Bcl-2、Bax和Caspase-3的蛋白表达水平.结果表明，与阴性对照组相比，不同染毒组、DBP组大鼠的学习记忆能力下降，氧化应激水平上升，且随DBP染毒浓度升高而加剧（p<0.05，p<0.01）；AD+25 mg·kg^-1·d^-1 DBP组较AD模型组大鼠的学习记忆能力损伤加剧，氧化应激水平和Bcl-2/Bax/Caspase-3信号通路上调，差异具有统计学意义（p<0.05）.由此推测，DBP可通过氧化应激作用，上调Bcl-2/Bax/Caspase-3信号通路，加剧AD大鼠海马组织的损伤，导致学习记忆能力下降.本文通过DBP影响AD大鼠学习记忆能力的分子机制研究，揭示了氧化应激对凋亡信号通路的作用，并为进一步研究DBP的毒性提供了理论和数据依据.

• Abstract：To investigate molecular mechanism of learning and memory ability affected by dibutyl phthalate (DBP) in rats with Alzheimer's disease (AD), 56 female Wistar rats aged 5~6 weeks with SPF grade were randomly divided into 7 groups on average:Saline group; DBP 0.25 group; DBP 2.5 group; DBP 25 group; DBP 250 group; AD group and AD+DBP group. The results of Morris water maze were observed after continuous intragastric administration for 28 days. And the concentrations of reactive oxygen species (ROS), reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHDG) in the hippocampus were monitored. The transcriptional levels of Bcl-2, Bax and Caspase-3 mRNA were analyzed by real-time fluorescence quantitative PCR (qPCR). Western blot was used to detect the protein expression levels of Bcl-2, Bax and Caspase-3. Results showed that, compared with the Saline group, the learning and memory ability of rats in the different exposure groups gradually decreased, the levels of oxidative stress increased, with the increasing concentration of DBP (p<0.05, p<0.01). Compared with the AD group, rats in the AD+DBP group showed aggravation of learning and memory impairment, up-regulation of oxidative stress level and Bcl-2/Bax/Caspase-3 signaling pathway, with statistically significant difference(p<0.05). Thus, it is concluded that DBP can up-regulate the Bcl-2/Bax/Caspase-3 signaling pathway through oxidative stress, aggravate the damage of hippocampus in rats with Alzheimer's disease, and lead to the decline of learning and memory ability. Results of this study reveals the effect of oxidative stress on the apoptotic signaling pathway, and provide theoretical and data basis for further study on the toxicity of DBP.

• Key words：dibutyl phthalate(DBP)  Alzheimer's disease(AD)  oxidative stress  learning and memory ability  hippocampus

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