氟、砷染毒大鼠脑组织神经细胞损伤的实验研究

A research on damage of the brain nerve cells of rat caused by fluoride-arsenic exposure

目的探讨氟、砷对大鼠学习记忆能力及大脑组织神经细胞损伤的影响。方法 90只初断乳清洁级SD大鼠随机分为9组,每组10只,雌雄各半,分别为对照(蒸馏水)组、低剂量砷(NaAsO_2 0.75mg/kg体质量)染毒组、高剂量砷(NaAsO_2 1.5 mg/kg体质量)染毒组、低剂量氟(NaF 25 mg/kg体质量)染毒组、高剂量氟(NaF 50mg/kg体质量)染毒组、低剂量砷(NaAsO_2 0.75 mg/kg体质量)与低剂量氟(NaF 25 mg/kg体质量)联合染毒组、低剂量砷(NaAsO_2 0.75mg/kg体质量)与高剂量氟(NaF 50 mg/kg体质量)联合染毒组、高剂量砷(NaAsO_2 1.5mg/kg体质量)与低剂量氟(NaF 25mg/kg体质量)联合染毒组及高剂量砷(NaAsO_2 1.5 mg/kg体质量)与高剂量氟(NaF 50mg/kg体质量)联合染毒组。自由饮水方式进行染毒,连续染毒6个月。采用Morris水迷宫实验评价大鼠学习记忆能力;透射电镜观察脑组织细胞超微结构改变;单细胞凝胶电泳法检测细胞DNA损伤情况。结果与对照组相比,高剂量砷、高剂量氟及高剂量氟砷联合染毒组大鼠逃避潜伏期明显延长;大脑皮质神经细胞出现皱缩、细胞核明显变形、核内染色质分布不均匀、胞浆内部分线粒体肿胀、内质网扩张等结构改变;并且脑组织神经细胞Olive尾矩值明显增高。结论氟、砷可透过血脑屏障在大鼠脑组织中蓄积,引起脑组织细胞形态学变化及神经细胞DNA损伤,这可能是氟、砷对动物学习记忆能力产生影响的重要原因。

Objective To observe the toxic effects of fluoride,arsenic and co-exposure on learning and Memory ability,ultrastructural changes and DNA damage in cerebral coaex in rats.Methods A total of 90 SD rats were randomly divided into 9groups by two-factors and three-levels factorial experiment design,10 rats in each group,control group（distilled water）,low dose NaAsO_2 （0.75 mg/kg）group,high dose NaAsO_2 （1.5mg/kg）group,low dose NaF（25 mg/kg）group,high dose NaF（50 mg/kg）group,low dose NaAsO_2 （0.75mg/kg）and low dose NaF（25mg/kg）combined group,low dose NaAsO_2 （0.75mg/kg）and high dose NaF（50mg/kg）combined group,high dose NaAsO_2 （1.5 mg/kg）and low dose NaF（25mg/kg）combined group,high dose NaAsO_2 （1.5 mg/kg）and high dose NaF（50 mg/kg）combined group.After 6months of exposure,learning ability was tested by the Morris water maze;ultrastructural changes of neurons in the cerebral cortex were observed by transmission electron microscope;DNA damage was detected by single cell gel electrophoresis（SCGE）.Results Compared with the control group,the escape latency periods of rats exposed to high-dose NaAsO_2 group,high-dose NaF group,highdose NaAsO_2 and high-dose NaF combined group were significantly prolonged in water maze test;The ultrastructure of cortex neurons also had pathological changes;and the olive tail moment in those groups were remarkably elevated.Conclusions Fluoride and arsenic could pass blood-brain barrier and cumulate in cerebral cortex of rats.Chronic fluoride,arsenic and fluoride-arsenic combined exposure may affect learning and memory abilities through cell pathological changes and DNA damage of brain nerve cells.