氟暴露对子代大鼠甲状腺激素水平改变及智力损伤的影响

Effects of fluoride exposure on thyroid hormone level and intelligence in rats

目的 研究氟暴露是否干扰大鼠甲状腺激素水平,探索高氟智力损伤的生物标志物.方法 选取清洁级SD健康大鼠24只,按体重随机分为对照组（自来水,氟含量为0.344 mg,/L）和低、中、高氟组（含氟化钠10、50、100 mg/L的自来水）,同组雌雄大鼠按2∶1合笼.至子代大鼠断乳后,每组选取体重相近的12只子代大鼠,雌雄各半,接受与亲代相同的处理,子代大鼠出生后第60天处死.测量子代大鼠体重,采用酶联免疫吸附法测定血清促甲状腺激素（TSH）、游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）水平,采用Morris水迷宫检测子代大鼠的学习记忆能力,采用蛋白印迹法检测血液淋巴细胞分裂蛋白1（Fis1）及线粒体融合蛋白1（Mfn1）的表达情况.结果 中、高氟组子代大鼠TSH、FT4含量明显低于对照组,差异均有统计学意义（P＜0.05）;定位航行实验中,中、高氟组子代大鼠所用时间长于对照组,高氟组所用路程长于对照组,差异均有统计学意义（P＜0.05）;空间探索实验中,低、中和高氟组子代大鼠在目标象限的时间（路程）/总时间（路程）明显少于对照组,差异均有统计学意义（P＜0.05）.与对照组相比,低、中、高氟组子代大鼠淋巴细胞Fis1表达增加,低、中氟组Mfn1表达增加,差异均有统计学意义（P＜0.05）.结论 高氟干扰甲状腺激素分泌,而外周淋巴细胞线粒体动力学异常为寻找氟致智力损伤的生物标志物提供线索.

Objective To investigate the effects of fluoride exposure on the thyroid hormone level and intelligence in rats and to investigate the biomarkers of intellectual impairment induced by high fluoride exposure.Methods A total of 24 clean healthy Sprague-Dawley rats were randomly divided into control group （tap water containing 0.344 mg/L fluoride） and low-,medium-,and high-fluoride exposure groups （tap waters containing 10,50,and 100 mg/L sodium fluoride,respectively）.One male rat was cohabited with two female rats in the same group.After the offspring rats were weaned,12 offspring rats （male/female ratio=1∶1） with a similar body weight in each group were subjected to the same treatment for the parental offspring.The offspring rats were sacrificed on the 60th day after birth.The weight of offspring rats was measured.Serum thyrotropin （TSH）,free triiodothyronine （FTs）,and free thyroxine （FT4） levels were measured by enzyme-linked immunosorbent assay.The learning and memory abilities of the rats were evaluated by Morris water maze test.The expression of mitochondrial fission 1 （Fis1） and mitofusin 1 （Mfn1） in blood was measured by Western blot.Results The offspring rats in the medium-and high-fluoride exposure groups had significantly lower serum TSH and FT4 levels than those in the control group （P〈0.05）.The place navigation test showed that the offspring rats in the medium-and high-fluoride exposure groups had significantly longer escape latency than those in the control group （P〈0.05）,and the high-fluoride exposure group had a significantly longer escape distance than those in the control group （P〈0.05）.The spatial probe test showed that the offspring rats in the low-,medium-,and high-fluoride exposure groups had significantly shorter swimming time and distance in the target quadrant and total swimming time and distance than those in the control group （P〈0.05）.Compared with the offspring rats in the control group,those in the low-,medium-,and high-fluoride exposure groups had significantly higher expression of Fis1 （P〈0.05）,and those in the low-and medium-fluoride exposure groups had significantly higher expression of Mfn1 （P〈0.05）.Conclusion High fluoride exposure can reduce the secretion of thyroid hormone and the abnormality of mitochondrial dynamics in peripheral lymphocytes may provide a clue to identifying the biomarkers of intellectual impairment induced by fluoride exposure.