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目的探讨铅暴露对小鼠学习记忆能力及海马组织中β-淀粉样前体蛋白(β-Amyloid Precursor Protein,β-APP)表达的影响。方法采用自由饮水模式建立铅暴露动物模型,将40只21日龄小鼠随机分为低、中、高剂量染毒组和对照组,分别饲以2 g/L,4 g/L,6 g/L的乙酸铅水溶液和去离子水。3个月后,Morris水迷宫试验测定小鼠学习记忆能力,石墨炉原子吸收光谱仪测定血液和海马中铅含量,wstern blot技术检测各组小鼠海马组织中APP蛋白的表达情况。结果与对照组相比,各剂量铅暴露组小鼠逃避潜伏期差异有统计学意义(P<0.05),随暴露剂量的增大而延长。与对照组相比,中、高剂量组穿越平台的次数明显减少(P<0.05),差异有统计学意义;各剂量铅暴露组血铅及海马铅含量与对照组相比,差异均有统计学意义(P<0.05),其中高剂量暴露组血铅和海马铅含量均高于其他各剂量暴露组,差异具有统计学意义(P<0.05);各剂量铅暴露组APP蛋白的表达量明显高于对照组,差异具有统计学意义(P<0.05),并随染毒剂量增加,表达量增高。结论铅可能诱导APP蛋白的过度表达造成神经系统损伤,从而影响小鼠学习记忆能力,这可能是铅致小鼠认知功能障碍的机制之一。
Objective To investigate the effects of lead exposure on learning and memory and the expression of β-amyloid precursor protein (β-APP) in hippocampus of mice. Methods The animal model of lead exposure was established by free drinking water. 40 21-day-old mice were randomly divided into low, medium and high dose exposure groups and control groups. The animals were fed with 2 g / L, 4 g / L, 6 g / L aqueous lead acetate solution and deionized water. Three months later, Morris water maze test was used to determine the learning and memory ability of mice. The content of lead in blood and hippocampus was determined by graphite furnace atomic absorption spectrometry. The protein expression of APP in hippocampus was detected by Western blot. Results Compared with the control group, the escape latency of mice in each dose of lead exposure group was significantly different (P <0.05), and prolonged with the increase of exposure dose. Compared with the control group, the number of medium and high dose groups across the platform was significantly reduced (P <0.05), the difference was statistically significant; lead and lead exposure of each dose of lead and hippocampus compared with the control group, the differences were statistically (P <0.05). The content of lead in hippocampus and hippocampus in high-dose exposure group were higher than those in other exposure groups (P <0.05). The expression of APP protein in each dose of lead exposure group was significantly Higher than the control group, the difference was statistically significant (P <0.05), and with the dose increased, the expression increased. Conclusion Lead may induce the damage of nervous system by inducing APP protein overexpression, which may affect the ability of learning and memory of mice, which may be one of the mechanisms of cognitive dysfunction induced by lead in mice.