目的观察氯化镧(LaCl3)对仔鼠学习记忆及蛋白激酶A-环腺苷酸反应元件结合蛋白(PKA—CREB)信号转导通路的影响。方法将60只Wistar雌性大鼠随机分为对照组(饮用蒸馏水)和低、中、高剂量染镧组(分别饮用含有0.25%、0.5%和1.0%LaCl,的蒸馏水溶液),每组15只。染镧组仔鼠在断乳前经由母体血循环和吸吮母乳染镧,断乳后则通过自行饮水摄入。至断乳后1个月结束,每组随机选择15只仔鼠进行水迷宫试验,并测定海马PKAc-α和p-CREB蛋白的表达水平。结果水迷宫试验中,各染镧组仔鼠与对照组比较,寻找平台的逃避潜伏期和游泳距离均增大,穿过目标平台的次数均减少,差异有统计学意义(P〈0.05)。各染镧组仔鼠海马PKAc-α和P—CREB蛋白的表达水平均低于对照组,差异有统计学意义(Pl〈0.05)。结论LaCl3可造成仔鼠的空间学习记忆损伤,抑制PKA—CREB信号转导通路。
Objective To observe the effect of lanthanum chloride (LaCl3) on learning and memory, and to discuss the influence of PKA-CREB signal transduction pathway on LaCl3-induced effect in offspring rats. Methods Sixty female Wistar rats were randomly divided into control (drank distilled water), low-, moderate-, and high-dose LaCl3 groups (drank 0.25%, 0.5% and 1.0% LaCl3 distilled water, respectively). The pregnant rats were administrated with LaCl3 in drinking water from day 0 of pregnancy to one month after weaning of offspring. The ability of learning and memory of offspring rats was evaluated with Morris water maze. PKA and p-CREB protein expression in the hippocampus of offspring rats was determined with Western blot respectively. Results The escape latency of three LaCl3-administrated groups were significantly longer than that of control group (P〈0.05). With the increase of LaCI3 dose, the swimming distance increased significantly (P〈0.05). The numbers of entering to the target quadrant and the protein expression of PKA and p-CREB decreased significantly (P〈0.05). Conclusion LaCl3 may inhibit PKA-CREB signal transduction pathway and have adverse effects on learning and memory in offspring rats.