高氟对大鼠甲状腺功能和脑损伤的影响

目的 观察高氟对大鼠甲状腺功能和脑损伤的影响.方法 将36只成年Wistar大鼠按性别和体质量随机分为3组:对照组、高氟组、高氟+甲状腺片组,每组12只,分别饮用自来水(含氟量<5 mg/L),加入100、100 ms/L氟化钠(NaF)的自来水:喂养7个月后高氟+甲状腺片组大鼠另给予0.04%甲状腺片(1.8ml·kg~(-1)·d~(-1))灌胃3周.喂养7个月零3周时,用放射免疫法测定各组大鼠血清TT_3、TT_4;光镜下观察大鼠甲状腺和脑组织形态结构;免疫组化方法检测海马区域NMDAR2B蛋白表达.结果 与对照组[(0.97±0.15)、(84.03±12.45)nmol/L]比较,高氟组大鼠血清TT_3、TT_4明显降低[(0.24 ±0.07)、(15.16±2.08)nmoL/L,P均<0.01];高氟+甲状腺片组与对照组比较,未见明显改变[(1.02 ±0.19)、(85.63±9.55)nmoL/L,P均>0.05],与高氟组相比较,明显增高(P均<0.01).光镜下高氟组可见甲状腺部分滤泡上皮增生、排列紊乱、萎缩,滤泡腔内胶质减少,而高氟+甲状腺片组与高氟组比较,甲状腺滤泡上皮增生程度减轻;高氟组海马神经元细胞肿胀、排列紊乱,高氟+甲状腺片组海马神经元细胞较高氟组肿胀减轻、排列有序.高氟组海马CA1、CA3区NMDAR2B阳性细胞灰度值(167.05±7.31)较对照组(92.53±9.67)和高氟+甲状腺片组(101.66±12.21)明显增高(P均<0.01).结论 高氟可导致成年大鼠甲状腺功能降低、形态改变,并引起大脑病理损害;在高氟损伤基础上给予甲状腺制剂替代后,大鼠甲状腺功能和形态可基本恢复正常,脑组织损伤明显减轻.慢性氟中毒造成的甲状腺功能降低可能是高氟造成脑损伤的另一重要参与因素.

Influence of high-fluoride on thyroid function and brain damage in rats

Objective To study the influence of high-fluoride on thyroid function and brain damage. Methods Thirty-six Wistar rats were randondy divided, according to weight and gender into 3 groups(12 rats each), i.e. control group, high fluoride group, and high fluoride plus thyroid tablet treatment group. The rats were fed with normal tap water containing no more than 5 mg/L NaF and the tap water added 100,100 mg/L NaF, respectively. After 7 months of experiment, the rats in high fluoride plus thyroid tablet treatment group were given with 0.04% thyroid tablet( 1.8 ml·kg~(-1)·d~(-1)) by gastric perfusion for three weeks. The contents of TT_3 and TT_4 in serum were detected by radio-immunological assay; the histomorphology in thyroids and brains were observed under microscopy; and the protein level of NMDAR2B subunit of glutamate receptor in the hippocampal CA1 and CA3 was measured by immunohistochemistry. Results As compared to the values of TT_3 and TT_4 in serum of rats in control group[ (0.97 ± 0.15), (84.03 ± 12.45)nmol/L], TT_3 and TT_4 in high fluoride group were obviously lower [(0.24 ± 0.07), (15.16 ± 2.08)nmol/L, all P < 0.01]; while no changes in TT_3 and TT_4 were detected in high fluoride plus thyroid tablet treatment group[ (1.02 ± 0.19), (85.63 ± 9.55)nmol/L, all P < 0.05] as compared to controls, but higher than those in high fluoride group(all P < 0.01 ). The pathological changes including partial hyperplasy, arrangement disorder, atrophy, and decreased colloid of the thyroid follicular epithelial cells in high fluoride group were observed under microscopy. In high fluoride plus thyroid tablet treatment group, the degree of the thyroid cellular hyperplasy was relatively slight as compared to high fluoride group. The swelling and disarrangement of neurons in the hippocampus were observed in high fluoride group, whereas the changes of the neurons were not so obvious in high fluoride plus thyroid tablet treatment group. The grey values of NMDAR2B positive cells in the hippocampal CA1 and CA3 in high fluoride group(167.05 ± 7.31 ) were significantly increased as compared to controls (92.53 ± 9.67 ) or high fluoride plus thyroid tablet treatment group( 101.66 ± 12.21, all P < 0.01 ). Conclusions High fluoride can induce the decreased function and changed histomorphology in thyroid and result in pathological damages in the brains of rats. However, treated with thyroid tablet to those having damages induced by high fluoride, the thyroid function and morphology can be normal, and the brain damages can be alleviated. The results indicate that hypothyroidism caused by high fluoride might be an important participating factor in brain damages caused by fluorosis.