乙酰柠檬酸三丁酯围产期暴露对子代小鼠认知能力的影响
Effects of Perinatal Exposure of Acetyl Tributyl Bitrate on Cognitive Ability of Offspring Mice
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摘要: 研究不同剂量的增塑剂乙酰柠檬酸三丁酯（acetyl tributyl citrate，ATBC）围产期暴露对子代小鼠认知能力的影响及其机制。以C57BL/6小鼠为受试动物，小鼠合笼后，对受孕雌性小鼠进行随机分组，设置对照组、ATBC暴露组（2、20和200 mg·kg-1·d-1），在围产期每天进行灌胃暴露。通过Morris水迷宫实验和跳台实验对子代小鼠的认知能力进行检测，观察子代小鼠脑组织病理变化及胶质细胞激活情况。检测子代小鼠脑组织匀浆中神经递质5-羟基色胺（5-hydroxytryptamine，5-HT）、乙酰胆碱（acetylcholine，ACh）、活性氧（reactive oxygen species，ROS）、丙二醛（malondialdehyde，MDA）和还原型谷胱甘肽（glutathione，GSH）、超氧化物歧化酶（superoxide dismutase，SOD）等的含量或活性以及肿瘤坏死因子α（tumor necrosis factor α，TNF-α）、白介素17（interleukin-17）的水平。结果显示，200 mg·kg-1·d-1的ATBC围产期暴露会导致子代小鼠认知能力下降，脑海马结构出现改变，胶质细胞活化程度增大，脑组织氧化应激水平上升，促炎症因子TNF-α和IL-17含量增加。研究表明，200 mg·kg-1·d-1 ATBC围产期暴露可引起子代小鼠脑组织氧化应激，进而导致其认知能力下降。Abstract: To investigate the effects of perinatal exposure of acetyl tributyl citrate (ATBC) on cognitive ability of offspring mice and the possible mechanism, C57BL/6 mice were used as experimental animals. Male mice were mated with female mice, the pregnant females were randomly divided into four groups and orally administered with drugs daily for the whole perinatal period. The groups were control group, ATBC exposure groups (2, 20 and 200 mg·kg-1·d-1). The cognitive ability of offspring mice was detected by Morris water maze test and step-down passive avoidance test, and the pathological changes of brain tissue and glial cell activation of offspring mice were observed. The content of 5-hydroxytryptamine (5-HT), acetylcholine (ACh), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor α (TNF-α), interleukin 17 (IL-17) and the activity of superoxide dismutase (SOD) in offspring mice brain were detected. The results showed that perinatal exposure of ATBC at 200 mg·kg-1·d-1 induced cognitive decline of offspring mice, structural changes of hippocampus, increased the glial cells activation levels and oxidative stress level of offspring mice brain tissue. Meanwhile, the levels of proinflammatory cytokines TNF-α and IL-17 were also increased. Studies show that 200 mg·kg-1·d-1 ATBC perinatal exposure can cause oxidative stress in the brain tissues of offspring mice, leading to a decline in their cognitive ability.
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