中文摘要：

目的通过观察慢性氟中毒大鼠脑组织中细胞外调节蛋白激酶5（extracellular-signalregulatedkinase5，ERK5）的表达与活性，及与大鼠学习记忆能力变化的关系，深入探讨慢性氟中毒神经系统损害的发病机制。方法30只SD大鼠按体质量采用随机数字表法分为3组，每组10只，雌雄各半。对照组自由饮用自来水（含氟量〈0．5mg／L），低氟组、高氟组饮水含氟量分别为10．O、50．0mg／L。实验6个月后，取大鼠脑组织，实时荧光定量PCR（real．timePCR）检测ERK5的mRNA表达水平。蛋白免疫印迹法检测细胞外ERK5的蛋白表达水平及活性；Morris水迷宫检测慢性氟中毒大鼠学习记忆能力。结果低氟组、高氟组大鼠出现不同程度的氟斑牙，且随着染氟剂量的升高大鼠尿氟含量逐渐升高（F=164．10，P〈0．05）。对照组、低氟组、高氟组大鼠脑组织磷酸化（p）．ERK5蛋白水平分别是0．13±0．03、0．29±0．10、0．43±0．17，组间比较差异有统计学意义（F=11．96，P〈0．05），其中低氟组、高氟组高于对照组（JP均〈0．05）；总．ERK5蛋白水平分别是0．32±0．11、0．37±0．13、0．49±0．16，各组间比较差异有统计学意义（F=3．45，P〈0．05），其中高氟组高于对照组（P〈0．05）。大鼠脑组织ERK5mRNA表达水平组间比较差异无统计学意义（F=0．81，P〉0．05）。定向航行实验第2、3、4天，大鼠逃避潜伏期、穿越平台次数组间比较差异均有统计学意义（H=28．20、29．90、26．47，27．23、35．34、27．62，P均〈0．01）；第5天空间探索实验，大鼠第1次穿越平台时间、穿越平台次数组间比较差异均有统计学意义（H=31．41、30．80，P均〈0．01）。大鼠脑组织p-ERK5蛋白表达水平与大鼠第5天穿越平台次数呈负相关（r=-0．470，P〈0．01），而与大鼠第5天第1次穿越平台时间呈正相关（r=0．591，P〈0．01）。结论慢

英文摘要：

Objective Through observation of the expression and activity of extraeellular regulated protein kinase 5 （ERKS） and its relationship with the learning and memory ability in rats with chronic fluorosis, to further study the pathogenesis of chronic fluorosis in nervous system. Methods Thirty SD rats were divided into 3 groups according to body weight by means of a random number table （10 rats in each group, half male and half female）. The rats in control group were fed with free drinking tap water containing less than 0.5 mg/L fluoride （NaF）; the rats in low fluoride group with 10.0 mg/L fluoride; the rat in high dose fluoride group with 50.0 mg/L fluoride. After 6 months of experiment, rat brain tissue was took, mRNA expression level of ERK5 was detected by real-time fluorescence quantitative PCR （real-time PCR）, protein expression level and activity of ERK5 were detected by Western blotting; the learning and memory ability of rats with chronic fluorosis were detected by Morris water maze test. Results The rat in groups exposed to fluoride exhibited different degrees of dental fluorosis and the fluoride content in urine of rats increased gradually with increase of fluoride doses （F = 164.10, p 〈 0.05）. The protein levels of phosphor-ERK5 in the control group, low fluoride group and high fluoride group were 0.13±0.03, 0.29± 0.10 and 0.43± 0.17, respectively, the difference was statistically significant （F = 11.96, P 〈 0.05）, and low fluoride group and high fluoride group were higher than control group （all P 〈 0.05）. The total protein levels of ERK5 in control group, low fluoride group and high fluoride group were 0.32 ± 0.11, 0.37± 0.13 and 0.49 ± 0.16, respectively, the difference was statistically significant （F = 3.45, P 〈 0.05）, and high fluoride group was higher than control group （P 〈 0.05）. The expression of ERK5 mRNA in rat brains between groups was not significantly different （F = 0.81, P 〉 0.05）. The second, third, and forth days of directional na