发育期铅暴露对仔鼠海马Homer表达和学习记忆影响

目的 探讨发育期慢性低浓度铅暴露对仔鼠海马Homer1b/c蛋白表达变化与学习记忆能力的关系。方法 30只孕鼠按体重随机分为3组,分别给予双蒸水(对照组)、0.05%、0.20%醋酸铅饮水(低、高剂量染铅组),断乳后仔鼠自行饮用含铅水至生后28 d,生后56 d采用跳台试验测试仔鼠学习记忆能力;Western blot法检测仔鼠生后7、14、21、28 d海马Homer1b/c蛋白表达;血铅和海马脑铅含量用原子吸收光谱法测定。结果 对照组、0.05%、0.20%醋酸铅组仔鼠跳台试验逃离潜伏期分别为(25.71±4.56)、(39.67±5.18)、(64.82±9.73) s,停留潜伏期分别为(234.89±25.85)、(147.15±19.26)、(83.56±14.52)s,与对照组比较,各剂量染铅组仔鼠逃离潜伏期明显延长、停留潜伏期明显缩短(P<0.05);与对照组比较,生后7、14、21、28 d时,0.05%和0.20%醋酸铅组仔鼠海马Homer1b/c蛋白表达分别为(0.607±0.022)、(0.825±0.054)、(0.583±0.015)、(0.557±0.011)和(0.540±0.021)、(0.574±0.018)、(0.471±0.009)、(0.412±0.007)明显降低(P<0.05)。结论 慢性铅暴露可降低仔鼠被动回避反应的学习和记忆能力,其机制可能与染铅所致仔鼠海马Homer1b/c蛋白表达下降有关。

Effects of lead exposure on Homer1b/c expression in hippocampus and on learning and memory in offspring rats

Objective To observe the effect of low level lead exposure during pregnant on the expression of Homer1b/c in hippocampus and the relationship between the exposure and learning and memory in offspring rats.Methods Thirty pregnant rats were randomly divided into 3 groups:a control group fed with doubly distilled water and two treatment groups exposed to 0.05% and 0.2% lead acetate(PbAc) in drinking water during pregnancy and lactation. After weaning, the offspring rats of treatment groups were directly fed with drinking water to postnatal 28 day as their dams.Step-down test was used to observe the change in learning and memory for passive avoidance response at postnatal 56 days.Western blot was used to detect the protein expression of Homer1b/c in hippocampus of offspring rats at postnatal 7, 14, 21, and 28 day, respectively.The contents of lead in blood and hippocampus were determined with atomic absorption spectrophotometer at postnatal 28 days.Results Compared to the controls, the offspring rats exposed to 0.05% and 0.2% PbAc showed significantly longer average escaping latency(39.67±5.18 and 64.82±9.73 vs. 25.71±4.56 seconds) and significantly shorter average remaining latency(147.15±19.26 and 83.56±14.52 vs. 234.89±25.85 seconds) (all P<0.05).The expressions of Homer1b/c in hippocampus of the offspring rats exposed to 0.05% and 0.2% PbAc were 0.607±0.022, 0.825±0.054, 0.583±0.015, and 0.557±0.011and 0.540±0.021, 0.574±0.018, 0.471±0.009, and 0.412±0.007 at postnatal 7, 14, 21, and 28 day, with a decreased tendency compared to those of the control group(P<0.05).Conclusion Chronic lead exposure results in decreases of ability of learning and memory for passive avoidance response in offspring rats and the effect may relate to the decline of homer1b/c expression in hippocampus in rats.