孕鼠慢性砷暴露对胎鼠脑组织DNA的损伤和子代记忆功能的影响

目的:通过观察孕鼠慢性砷暴露对胎鼠脑组织DNA的损伤和子代记忆功能的影响,为探讨砷对胎儿的神经毒作用机制提供依据。方法:雌性小鼠受孕后第2天开始以自由饮水方式分别暴露于0ppm(对照组)、2ppm、4ppm的As2O3水溶液,连续染毒直到仔鼠出生,饲养48天,每组随机取仔鼠10只,雌雄各半,共30只,利用Morris水迷宫定向航行实验连续观察5天,每天观察3次,测定小鼠的逃避潜伏期。另取同窝别30只新生小鼠断头处死并立即取脑固定,用免疫组化方法观察脑组织神经细胞中8-羟基脱氧鸟嘌呤(8-OHdG)的表达。结果:Morris水迷宫实验结果表明,第1、3、5天,4ppm染砷组小鼠的逃避潜伏期显著长于对照组(P<0.01)。而且第3天,该染砷组小鼠的逃避潜伏期也显著长于2ppm染砷组(P<0.05)。2ppm染砷组小鼠的逃避潜伏期与对照组比较均无显著性差异。染砷组仔鼠脑皮质神经细胞中8-OHdG呈现高表达,尤其4ppm染砷组仔鼠脑皮质神经细胞中的8-OHdG表达显著高于其他两组。结论:孕鼠慢性砷暴露可引起子代小鼠神经组织DNA的氧化损伤,并且影响子代小鼠的记忆功能。

Influence of chronic exposure of pregnant mice to arsenic on DNA damage in embryo mice and memory function of young generation

Objective:To observe the Influence of chronic exposure of pregnant mice to arsenic on DNA damage in embryo mice and memory function of young generation and to provide evidences for exploring mechanism of arsenic toxicity to embryo mice.Methods:On the second day of pregnancy,the pregnant mice were divided into 2 experimental groups,e.g.2 ppm As2O3 and 4 ppm As2O3 groups and one controls.As2O3 was administered to pregnant mice ad libitum in water for consecutive till young mouse born,each grouPtakes 10 young mice,female and male is half and half,30 in total.Expression of 8-hydroxy-2'-desoxyguanosine(8-OHdG) as biomarker of DNA damage in brain was observed immediately after embryo mice born by immunohistochemistry.On 48 days after borning,memory function of young generation was examined 3 times everyday for 5 days using the Morris water maze.Results:The escaping potential time in mice was significantly longer in the grouPreceived to 4 ppm As2O3 than that in controls(P<0.01)in the observation of the first,third and fifth days,and the escaping potential time was also significantly longer in the former than grouPreceived 2 ppm As2O3 in the third day(P<0.05).There is not any significant difference in the escaping potential time between the grouPreceived 2 ppm As2O3 and controls.In brain tissue of mice,8-OHdG presents obvious high expression in the experimental groups.Especially,expression of 8-OHdG in the grouPreceived to 4 ppm As2O3 was significantly higher than those in the other two groups.Conclusions:Chronic arsenic exposure of pregnant mice may induce DNA damage in embryo and affect the memory function of young generation.