[目的]探讨铅(Pb)暴露对快速衰老小鼠(SAMP8)学习记忆能力的影响及其机制。[方法]雄性SAMP8小鼠及其野生型SAMR1小鼠各20只,各随机分为2组,即SAMR1组、SAMR1+Pb组和SAMP8组、SAMP8+Pb组。SAMR1+Pb组和SAMP8+Pb组小鼠每天饲以0.05 g/L醋酸铅饮用水,SAMR1组和SAMP8组小鼠每天饲以0.05 g/L醋酸钠饮用水,共饮水9周。应用Morris水迷宫实验检测小鼠学习记忆能力;采用免疫荧光法测定实验小鼠侧脑室下区(SVZ)淀粉样前体蛋白(APP)、神经元母细胞和星形胶质样细胞特异性标志物[双皮质素(DCX)、神经胶质纤维酸性蛋白(GFAP)]的表达情况,分析神经元母细胞和星形胶质细胞的细胞比率变化;应用实时荧光定量PCR检测实验小鼠SVZ中DCX、GFAP和脑源性神经营养因子(BDNF)的mRNA表达情况。[结果]小鼠Morris水迷宫实验第3天结果显示:与SAMR1组[(10.94±3.98)s]相比,SAMP8组[(29.24±6.15)s]、SAMR1+Pb组[(34.15±6.78)s]和SAMP8+Pb组[(50.86±8.56)s]的逃避潜伏期延长,差异有统计学意义(P〈0.05);且与SAMP8组和SAMR1+Pb组小鼠比较,SAMP8+Pb组小鼠的逃避潜伏期更长(P〈0.05)。SAMR1组、SAMP8组、SAMR1+Pb组和SAMP8+Pb组小鼠的平均穿越平台次数分别为(6.75±1.28)、(3.25±1.28)、(3.88±1.46)、(1.25±0.46)次;SAMP8组、SAMR1+Pb组和SAMP8+Pb组小鼠穿越次数较SAMR1组均减少(P〈0.05);SAMP8+Pb组小鼠穿越次数也明显低于SAMP8组和SAMR1+Pb组(P〈0.05)。免疫荧光法测定结果显示:与SAMR1组小鼠比较,SAMR1+Pb组、SAMP8组和SAMP8+Pb组小鼠SVZ区APP荧光强度分别上升了79%、53%和216%;与SAMR1+Pb组和SAMP8组比较,SAMP8+Pb组小鼠APP荧光强度分别上升了76%和107%,差异均具有统计学意义(P〈0.05)。与SAMR1组小鼠比较,SAMP8组和SAMP8+Pb组小鼠SVZ中GFAP(+)/DAPI(+)和DCX(+)/DAPI(+)细胞比率均降低,SAMP8+Pb组小
[ Objective ] To investigate the effects and related mechanism of lead (Pb) exposure on learning and memory ability of senescence accelerated mice (SAMP8) [ Methods ] Twenty male SAMP8 mice and 20 male SAMR1 mice were randomly divided into four groups: SAMR1, SAMRI+Pb exposure, SAMP8, and SAMP8+Pb exposure groups. Mice in the SAMRI+Pb exposure group and the SAMP8+Pb exposure group were treated with 0.05 g/L lead acetate via drinking water for nine weeks, and mice in the SAMR1 group and the SAMP8 group were given 0.05 g/L sodium acetate via drinking water for nine weeks. Morris water maze experiment was applied to test learning and memory ability. Protein expressions of amyloid precursor protein (APP), doublecortin (DCX), and glial fibrillary acidic protein (GFAP) in subventricular zone (SVZ) were observed by immunofluorescence, and the cell counts of neuronal progenitors and astrocytes were analyzed. The mRNA expressions of DCX, GFAP, and brain-derived neurophic factor (BDNF) in SVZ were detected by quantitative real-time PCR. [ Results ] The results of Morris water maze test on day 3 showed that, compared with the SAMR1 group [(10.94±3.98)s], the escape latencies of the SAMRI+Pb exposure group [(34.15±6.78)s], the SAMP8 group [(29.24±6.15)s], and the SAMP8+Pb exposure group [(50.86±8.56)s] were increased (P〈0.05); compared with the SAMP8 group and the SAMRI+Pb exposure group, the escape latency of the SAMP8+Pb exposure group was extented (P 〈 0.05); the number of platform crossings were 6.75± 1.28 in the SAMR1 group, 3.88 ±1.46 in the SAMRI+Pb exposure group, 3.25 ±1.28 in the SAMP8 group, and 1.25± 0.46 in the SAMP8+Pb exposure group; the numbers in the SAMRI+Pb exposure group, SAMP8 group, and SAMP8+Pb exposure group were lower than those in the SAMR1 group (P 〈 0.05); compared with the SAMP8 group and the SAMRI+Pb exposure group, the number in the SAMP8+Pb exposure group was also decreased (P〈 0.05). The