硒对饮水型氟中毒致脑损伤的干预分子机理研究

项目名称： 硒对饮水型氟中毒致脑损伤的干预分子机理研究

项目编号： No.30872195

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 章子贵

作者单位： 浙江师范大学

项目金额： 33万元

中文摘要： 选用初断乳SD雄性大鼠480只，在成功复制氟中毒动物模型基础上，采用先硒后氟、硒氟同喂和后氟后硒三种干预方式（治疗、拮抗和预防），用分子生物学的方法和技术，评价和探讨不同剂量硒（低硒：0.375 mg/L、中硒：0.75 mg/L、高硒：1.5 mg/L）对饮水型氟中毒（50mg/L）致脑损伤干预作用的效果及脑内分子机理。结果表明，慢性饮水型氟暴露对大鼠脑功能有损伤作用，其分子机理可能与脑海马内神经细胞分布稀疏、细胞轮廓消失等病理性变化、海马突触体膜流动性降低、海马突触体内PSD-93蛋白/基因上调和Ca2+超载、海马突触体内钙离子信号通路中NF-κρ蛋白表达升高有关，而一定浓度硒能显著改善饮水型氟致脑功能的损伤，并能逆转上述氟中毒所致脑海马内细胞形态和一些氟中毒敏感分子水平的异常变化，说明适量硒对饮水型氟致脑损伤有干预作用，但不同干预方式，其最佳干预浓度有所不同，低硒(0.375 mg/L) 对氟中毒致脑功能损伤有预防作用，高硒（1.5mg/L）有拮抗作用，中硒(0. 75 mg/L)则有较好的治疗效果； NF-κ#21644;PSD-93可能是硒干预氟神经性损伤潜在靶点。

中文关键词： 硒；氟中毒；脑损伤；干预作用

英文摘要： Based on copying fluorosis animal model，480 weanling male SD rats were treated by different intervention methods such as fluoride-after-selenium, fluoride+selenium and selenium-after-fluoride（treatment，antagonism and prevention），and then molecular biological me-thods and techniques were used to evaluate and investigate the inte-rvention effects of different concentrations of selenium（low seleniu-m：0.375 mg/L，middle selenium：0.75 mg/L，high selenium：1.5 mg/L） against drinking water fluorosis and the molecular mechani-sm in brain. The results show that brain functions of rats were da-maged by chronic fluoride exposure through drinking water，and themolecular mechanisms may be related to the pathological changes such as sparse distribution of nerve cells and disappearance of cell contours，the reduction of synaptosome membrane fluidity，the upregulation of synaptosome PSD-93 protein / gene，the synaptosome Ca2+ overload and the increased expression of synaptosome NF-κρ in hippocampus，a certain concentration of selenium can alleviate such damage in brain，reverse the abnormal changes of hippocampus cells'morphology and some fluoride-sensitive molecules'levels. All of these illustrate that appropriate amount of selenium have intervention effects on brain impairment induced by chronic fluorosis，but different concentrations of selenium and different feeding methods have different effects，low selenium has better preventive effect，high selenium has better antagonistic effect while middle selenium has better therapeutic effect；the changes of Ca2+ content may be a key link of nerve injury induced by chronic fluorosis and NF-κ#65292;PSD-93 may be the targets for selenium against damage induced by fluorosis.

英文关键词： Selenium；Fluorosis；Brain Injury；Intervention