目的探讨氯化镧暴露对仔鼠学习记忆能力的损伤作用及对ERK/CREB信号转导通路的抑制作用。方法将60只雌性Wistar大鼠随机分为对照(饮用蒸馏水)组和低(0.25%)、中(0.5%)、高(1%)浓度氯化镧染毒组。从雌鼠受孕第0天起通过自由饮水染毒至仔鼠断乳,仔鼠断乳后通过自由饮用与原剂量相同的氯化镧水溶液染毒至断乳后1个月。采用Morris水迷宫试验测定仔鼠的学习记忆能力,采用westernblot法测定仔鼠海马p-ERK1/2和p-CREB蛋白的表达水平。结果在定位航行试验和空间探索试验中,与对照组比较,不同浓度氯化镧染毒组仔鼠的逃避潜伏期和游泳距离均延长,在目标象限停留时间均缩短,差异有统计学意义(P〈0.05);且均具有剂量一反应关系(P〈0.05)。与对照组比较,不同浓度氯化镧染毒组仔鼠海马中p-ERK1/2、p-CREB蛋白的表达水平均降低,差异有统计学意义(P〈0.05);且随着氯化镧染毒浓度的升高,仔鼠海马中p-ERK1/2、p-CREB蛋白的表达水平均呈下降趋势。结论氯化镧可造成仔鼠的学习记忆损伤,其对于ERK/CREB信号转导通路的抑制可能是相关作用机制之一。
Objective To observe the effect of lanthanum chloride (LaC13) on learning and memory and ERK/CREB signal transduetion pathway in offspring rats. Methods Sixty female Wistar rats were randomly divided into control (drinking distilled water), low-, moderate-, and high-dose LaC13 groups (drinking distilled water containing 0.25%, 0.5% and 1% LaC13, respectively). The pregnant rats were given LaC13 through drinking water from the first day of pregnancy to weaning of offspring. The offspring rats were given the same doses of LaCl3 as their maternal rats through drinking water from weaning to one month later. Morris water maze was used to evaluate the ability of learning and memory of offspring rats. Western blot was used to analyze the protein expression of p-ERK1/2 and p-CREB in the hippocampus of offspring rats. Results In the orientate trials and probe trials, compared with the control group, the escape latency and pathlength of offspring rats in LaCl3-treated groups were longer, the dwell time in the target quadrant was significant shorter with a dose-dependent manner (P〈0.05). Compared with the control group, the protein expression of p-ERK1/2 and p-CREB in the hippocampus of offspring rats in LaCl3-treated groups decreased significantly (P〈0.05). With LaCl3 dose increased,the protein expression of p-ERK1/2 and p-CREB in the hippocampus of offspring rats decreased. Conclusion LaCl3 may cause the impairment of learning and memory in offspring rats,and one of mechanism underlying the effect may be the inhibition of ERK/CREB signal transduction pathway induced by LaCl3.