慢性氟中毒大鼠脑组织细胞外调节蛋白激酶表达及大鼠学习记忆能力的变化  

Modified expression o f extracellular signal-regulated protein kinase signal transduction in rat brains and changed capacity of learning and memory of rats with chronic fluorosis

作　　者：刘艳洁[1] 高勤[1] 吴昌学[2] 龙义国[1] 官志忠[1] 

机构地区：[1]贵阳医学院病理学教研室,550004 [2]贵阳医学院分子生物学实验室,550004

出　　处：《中国地方病学杂志》2009年第1期32-35,共4页Chinese Jouranl of Endemiology

基　　金：基金项目：科技部97项目（2006CB708513）;国家自然科学基金（30760224）;贵州省科技厅项目[黔科合外G字（2006400107）、黔省专合字（2006）52、黔科合重大专项（2006）6015]

摘　　要：目的观察慢性氟中毒大鼠脑组织中分裂原激活的蛋白激酶（MAPK）信号转导系统细胞外调节蛋白激酶（ERKI／2）的表达与活性，及其与学习记忆能力改变之间的关系，从而进一步探讨氟中毒神经系统损害的发病机制。方法72只SD大鼠按性别和体质量随机分为3组，每组24只。对照组：自由饮用自来水．含氟量低于0．5mg／L；低剂量染氟组：饮水含氟量为5．0mg／L；高剂量染氟组：饮水含氟量为50．0mg／L。实验6个月后，取大鼠脑组织，用蛋白印迹方法检测细胞外ERKI／2的蛋白表达与活性：用逆转录一聚合酶链反应（RT—PCR）方法测定ERKl／2的mRNA水平；用Morris水迷宫检测大鼠学习记忆能力改变。结果对照组、低、高剂量染氟组的ERKI／2蛋白水平分别为0．94±0．10、1．25±0．02、1．95±0．07，任意两组间比较．差异均有统计学意义（P〈0．05）；对照组、低、高剂量染氟组的phospho—ERKl／2蛋白水平分别为0．73±0．08、0．77±O．07、1．28±0．11，任意两组间比较，差异有统计学意义（P〈0．05）；低、高剂量染氟组的ERKl／2活化率『（68．4±3．8）％、（64．1±3．2）％]低于对照组[（823±10．7）％]，组间比较差异均有统计学意义（P〈O．05）；在第2、3、5、6天，低剂量染氟组的大鼠逃避潜伏期[（46．0±8．0）、（24．0±2．7）、（8．9±5．3）、（7．4±4．1）S]长于对照组『（39-3±6．9）、（19．1±9．1）、（8.3±3．4）、（4．8±2．7）S]，组间比较差异均有统计学意义（P〈0．05），高剂量染氟组的大鼠逃避潜伏期[（36．9±16．8）、（37．7±12．9）、（19．7±7．6）、（12．2±5．7）s]也长于对照组（P〈0．05），第3、5、6天，高剂量染氟组的大鼠逃避潜伏期长于低剂量染氟组（P〈0．05）；低剂量组、高剂量染氟组的大鼠第1次穿越平台位置时间[（1．17±0．75），（4Objective To investigate the expression of extracellular signal-regulated protein kinase （ERK1/2） pathway in rat brains with fluorosis and the effects of fluoride on learning and memory of the rats, and to reveal the mechanisms of damaged nervous system resulted from the toxicity of the ion. Methods Seventy-two SD rats were divided into 3 groups and 24 rats were in each group. Three groups were fed respectively with different concentrations of fluoride （ NaF ） for 6 months to establish rat models with fluorosis. Controls were fed with tap water （NaF 〈 0.5 rag/L） ; lower and higher concentration group were fed with water containing NaF（5, 50 mg/L）. Animals are sacrificed after 6 months of treatment with fluoride and the dissected brains were kept for analysis. The protein levels of ERK1/2 in rat brains were detected by Western-blotting and the mRNA level by RT-PCR. The spatial learning and memorizing ability was measured by Morris water maze test. Results The ERK1/2 protein in control group, lower and higher concentration group was 0.944 ± 0.10, 1.253 ± 0.02,1.953 ± 0.07, the differece being statistically sighificant between any two groups （P 〈 0.05）. The phospho-ERK1/2 protein in control group, lower and higher concentration group was 0.73 ± 0.08,0.77 ± 0.07,1.28 ± 0.11, the differece being statistically sighificant between any two groups（P 〈 0.05）; the activation rate of phospho-ERK1/2 in lower and higher concentration group [ （68.4 ± 3.8）%, （64.1 ± 3.2）% ] was decreased compared to control group [ （82.3 ± 10.7）%], the d iffereee being signifieant（P 〈 0.05）. In the navigation trial, longer escape lateneies of lower concentration group on the second, the third, the fifth and the sixth day were observed[ （46.0 ± 8.0）, （24.0 ± 2.7）, （8.9 ± 5.3）, （7.4 ± 4.1 ）s] compared to the control[ （39.3 ± 6.9）, （19.1 ± 9.1 ）, （8.3 ± 3.4）, （4.8 ± 2.7）s], the differeee being significant （P 〈 0.05 or 〈 0.01 ） ; the similar resu

关 键 词：氟化物中毒 学习 记忆 细胞外调节蛋白激酶 

分 类 号：R686[医药卫生—骨科学]