【作者】 葛亚明；

【导师】 王俊东； 庞全海；

【作者基本信息】 山西农业大学 ， 临床兽医学， 2003， 硕士

【摘要】 [目的]研究高氟、低碘导致学习记忆障碍的相关机制及氟碘相互作用的关系，为制定针对性的预防措施，减少氟中毒、低碘病的流行提供重要的理论依据。 [方法]采用低碘区粮食作为饲料，饮用100mg／L氟化钠去离子水，分别建立高氟、低碘、高氟低碘组Wistar大鼠，生产子代。在其0、10、20、30、60、90d时，采用被动回避实验（跳台法）检测大鼠学习记忆能力的改变，处死大鼠后，在对其脑组织形态进行观察的基础上，测定其相关生化指标。 [结果]相关分析表明：高氟、低碘对不同日龄大鼠学习记忆能力、脑组织病理形态以及神经生化指标的改变影响较大，尤其在大鼠发育期效果明显。 （1）高氟组和低碘组大鼠大脑皮质及海马内有较多神经元核固缩、核溶解及细胞轮廓不清晰。高氟低碘组，有大量神经元出现核固缩、核溶解、锥体突明显拉长等现象，并且在大鼠发育期内尤其明显。 （2）与正常组大鼠相比，各试验组大鼠在5min内学习错误次数（EN1）和24h后的5min内错误次数（EN2）均显著增加（P＜0.05）。被动回避的潜伏期时间均显著减少（P＜0.05）。高氟低碘组大鼠比高氟组、低碘组的EN1、EN2均显著增加，ST有不同程度的减少，但差异不显著（P＞0.05）。 （3）高氟组体重、TchE及MAO活性呈下降趋势，其中10日龄时体重降低显著；10、20和30日龄时TchE活性降低显著。脑重、MDA、H₂O₂、NO及总抗氧化能力呈先降低后升高趋势，其中10和20日龄时脑重降低明显（P＜0.05）；10日龄时MDA和H₂O₂显著升高（P＜0.05）；NO在10日龄升高及90日龄降低均显著（P＜0.05）。甲状腺、SOD、CAT和NOS呈先升高后降低的趋势，其中10日龄时甲状腺降低明显（P＜0.05）；NOS在0日龄时升高明显（P＜0.05），90日龄时降低显著（P＜0.05）。 （4）低碘组体重、脑重、蛋白含量及TchE和N0活性均呈下降趋势，其中10日龄时体重及0日龄时脑重均明显下降（P<0.05）;10、20日龄时蛋白含量、0和90日龄时TchE活性显著降低及10和20日龄N0活性均下降明显（P<0.05）.甲状腺重量、MDA含量、CAT和NOS活性呈先升高后降低趋势，其中，0、10、30日龄时MDA含量和0、10、60日龄时NOS活性均升高明显（P<0.05）;10和20日龄时CAT活性下降明显（P<0.05）.总杭氧化能力、SOD活性、H202含量呈现升高一降低一升高的变化趋势。 （5）高氟低碘组体重、脑重、甲状腺重、蛋白含量、H202含量、NOS活性均呈先升高后降低趋势，其中0日龄时体重及O、10、20、30日龄时蛋白含量明显降低（P<0.05）;20日龄时脑重和30、90日龄时NOS活性升高显著（P<0.05）:H202含量在20、30日龄时降低明显（P<0.05），60日龄时升高明显（P<0.05）.TchE、MAO及SOD活性呈先升高后降低趋势，其中TchE活性在10日龄时升高明显（P<0.05），30、60、90日龄时降低明显（P<0.05）:90日龄时MAO活性显著下降（P<0.05）:0、10、20、30日龄时SOD活性明显升高（P<0.05）。MDA含量呈升高趋势，其中20、30、60日龄时升高显著（P<0.05）。以T活性呈降低一升高一降低的变化趋势，其中在10、20、90日龄时均降低显著（P<0.05）。总杭氧化能力在0、20、60日龄时显著升高（P<0.05），10、30、90日龄时均降低，但差异不显著（P>0.05）。 [结论1（1）过量氟可损伤大鼠脑组织，影响其脑的发育，并且可加重碘的不足;（2）高氟、低碘对大鼠大脑作用时间应在大鼠脑发育期内或之前。 （3）氟碘通过多种机制影响脑的发育，干扰中枢神经递质的降解及转运过程，影响N0信使系统正常运行是其主要机制。更多还原

【Abstract】 [Objective] The mechanism of learning and memory impairment in rat induced by fluoride and iodine deficiency and correlation of fluoride and iodine were studied, to provide the important and scientific basis for the specific prevention of fluorosis and iodine deficiency.[Method] Filial generation of rats were used as experimental objections, which parents were Wistar rats treated with fluoride, iodine deficiency, and fluoride and iodine deficiency respectively. Groups fluoride drunk double-distilled water added NaF l00mg/L. Groups iodine deficiency fed forager from the area of low iodine. Groups fluoride and iodine deficiency drunk double distilled water added NaF l00mg/L and fed forager from the area of low iodine. When filial rats were at 0,10,20,60,90-day-age, the step-down test was performed to measure the learning and memory abilities of rats, and the changes of pathological state in cerebrum were observed by microscope. At the same time, some related biochemical items were detected.[Result] Rusults of analysis showed that fluoride and iodine deficiency had effects on learning and memory abilities, pathological state in cerebrum, and all neuro-biochemical items of rats at different ages. The effects were more significant at the stage of development.（1） There are a few of nerve cells , which are Chromatin dense stain, pyknosin, and cell figure eligible , in the cortex and hippocampus of brains of rats in groups fluoride and Groups iodine deficiency, there are Chromatin dense stain, pyknosin, and peak tree projecting elongate in the large of nerve cells of rats treated with fluoride and iodine deficiency , particular during the stage of development.（2） Contracted with normal rats, EN1 and EN2 of the experimental filial rats added significantly （P<0.05）. And ST reduced obviously （P<0.05）. EN1 and EN2 of the experimental filial rats in groups fluoride and iodine deficiency were the highest in all groups （P<0.05）. And ST reduced obviously （P>0.05 ）.（3） In the groups treated with fluoride, body weight, the activity of TchE and MAO were decreased. Body weight and the activity of TchE were obvious lower than the controls at 10-day-age （P<0.05）. Brain weight, MDA, H₂O₂, NO and the capacity of total antioxidation were decreased firstly, and then increased. Brain weights were decreased significantly at 10,20-day-age （P<0.05）. At 10,20-day-age, the change of brain weights was opposition. NO were decreased obviously at 10,90-day-age （P<0.05）. Thyroid gland weight, SOD, CAT and NOS were increased firstly, and then increased. And Thyroid gland weights were decreasedsignificantly at 10-day-age （F<0.05）; NOS were increased obviously at’ 0-day-age （P<0.01）. A day-age, the change of NOS was opposition.（4） In the groups done with low iodine, body weight , brain weight, the content of protein , the activity of TchE and NO were decreased. Body weight at 10-day-age and brain weight at 0-day-age were decreased significantly （P<0.05）; the content of protein at 10,20-day-age, the activity of TchE at 0,90-day-age and the activity of NO at 10,20-day-age were decreased obviously （P<0.05）. Thyroid gland weight, the content of MDA, CAT and the activity of NOS were increased firstly, then decreased. And the content of MDA at 0,10,30-day-age and the activity of NOS at 0,10,60-day-age were increased significantly （P<0.05）; The activity of CAT at 10,20-day-age were decreased obviously （P<0.05）. The capability of total antioxidation, the activity of SOD and the content of H₂O₂ showed the tendency: being increased-decreased-increased.（5） In the groups treated with high fluoride and low iodine, body weight, brain weight, Thyroid gland weight, the content of protein and H₂O₂, the activity of NOS showed being increased firstly, then being decreased. And the body weight at 0-day-age and the content of protein at 0,10,20-day-age were decreased significantly （P<0.05）; Brain weight at 20-day-age and the activity of NOS at 30,90-day-age were increased obviously （P<0.05）; The content of H₂O₂ were d更多还原