2009 - FX of F- on lactating dams - offspring thryoid - rat

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2009 - FX of F- on lactating dams - offspring thryoid - rat

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148. 赵娜;胚胎期及哺乳期高氟对发育甲状腺的影响及可能的机制研究[D];贵阳中医学院;2009年
https://cdmd.cnki.com.cn/Article/CDMD-1 ... 016318.htm
Zhao Na - "Possible mechanism of the effects of fluoride on the thyroid during embryonic development and lqctation" Guiyang Medical College (2009)

目的:过量摄入氟对机体几乎所有组织均可产生毒性作用,有资料报道:高氟可致甲状腺功能损害,形态损伤,本研究探讨高氟致亲代大鼠甲状腺损害后是否对子代大鼠甲状腺产生损害及探讨可能的损害机制。 方法:将30只Wistar大鼠随机分为正常亲代组(N组)10只、高氟亲代组(F组)20只。正常亲代组饮用自来水,高氟亲代组饮用含NaF 100mg/L高氟水;7个月后经检测证实高氟亲代组大鼠出现甲状腺功能低减后,两组大鼠分别雌雄交配产生子代大鼠(分别为n、f组);哺乳期间母鼠继续饮用高氟水,30天后分笼;两组子代大鼠均以自来水加正常饲料饲养,4个月后取材。放免法测定血清TT3,TT4;HE染色观察甲状腺形态结构;免疫组化方法检测甲状腺组织谷氨酸受体NR2B亚单位表达的改变。 结果:(1)血清TT3,TT4改变:高氟子代组(f组)TT3明显低于正常子代组(n组)(P0.05),TT4亦有降低趋势。(2)HE染色显微镜观察甲状腺形态结构改变:n组大鼠甲状腺滤泡上皮结构正常,排列有序,滤胞无增生或萎缩。f组均表现滤泡上皮增生,数量及层次增加,排列紊乱,细胞呈柱状或高柱状,甚至可向滤泡腔突出形成乳头;部分滤泡内胶质减少,滤泡腔空虚,红染均质胶状物减少;部分甲状腺组织坏死,结构破坏,细胞结构不清,核消失;部分间质血管扩张充血,管腔增大,充满;部分间质有炎细胞散在浸润;部分间质纤维组织呈灶性或弥漫性增生。(3)甲状腺组织内NMDA受体亚单位NR2B免疫组化染色发现,各组甲状腺均有NR2B受体的表达,NR2B受体免疫组化染色呈棕黄色,主要着色在甲状腺腺泡上皮细胞的胞膜及胞浆。测量各组平均光密度:正常亲、子代组分别为122.99±4.17,115.17±6.46,两组无差异性;高氟亲代组为169.32±15.21,高氟子代组为94.00±13.33;F组NR2B阳性细胞较N组显著减少,f组NR2B阳性细胞较n组显著增多,各组之间平均光密度均值FN/nf(P均0.01)。 结论: 1.亲代大鼠过度染氟可导致子代大鼠甲状腺功能低减、形态结构损伤。 2.子代大鼠出生后即使较长时间脱离高氟环境,甲状腺功能低减、形态结构损伤仍难以逆转。 3.上述结论提示在氟中毒病区,关注孕妇、胎儿和新生儿甲状腺功能都十分重要;脱离高氟环境的胎儿和新生儿的甲状腺功能也要引起我们的关注。由于以替代治疗纠正甲状腺功能低减是简便、易行、有效和相对安全的,故一旦发现甲状腺功能低减应及时以TH或甲状腺制剂进行替代治疗。 4.免疫组化染色发现大鼠甲状腺有NR2B受体表达。 5.亲代大鼠过度染氟可导致亲子两代甲状腺NR2B受体表达异常,这可能是谷氨酸兴奋性毒性的表现。 6.NR2B受体导致甲状腺损伤的机制可能构成氟中毒致组织损伤的重要机理。

Purpose: Excessive intake of fluoride can have toxic effects on almost all tissues of the body. There are data reports: high fluoride can cause thyroid function damage and morphological damage. This study explores whether high fluoride causes thyroid damage in parent rats and whether it affects offspring rats. The thyroid gland is damaged and the possible damage mechanism is discussed. Methods: Thirty Wistar rats were randomly divided into 10 normal parental group (N group) and 20 high-fluoride parental group (F group). The normal parental group drank tap water, and the high-fluoride parental group drank NaF 100mg/L high-fluoride water; after 7 months of testing, it was confirmed that the rats in the high-fluoride parental group had hypothyroidism, and the two groups of rats were mated with male and female to produce offspring. Rats (respectively group n and f); mother rats continued to drink high fluoride water during lactation and were separated into cages after 30 days; the offspring rats of the two groups were fed with tap water and normal feed, and the materials were taken after 4 months. Serum TT3 and TT4 were measured by radioimmunoassay; thyroid morphology and structure were observed by HE staining; immunohistochemical method was used to detect the expression of glutamate receptor NR2B subunit in thyroid tissue. Results: (1) Changes in serum TT3 and TT4: The TT3 of the high-fluoride progeny group (f group) was significantly lower than that of the normal progeny group (n group) (P0.05), and TT4 also had a decreasing trend. (2) HE staining microscope to observe the morphological and structural changes of the thyroid gland: the thyroid follicular epithelium of the rats in the n group was normal, arranged in an orderly manner, and there was no proliferation or atrophy of the filter cells. Group f showed follicular epithelial hyperplasia, increased number and levels, disordered arrangement, and the cells were columnar or tall columnar, and they could even protrude to the follicular cavity to form papillae; part of the follicles had reduced colloid, the follicular cavity was empty, and the red staining was uniform. Reduced jelly; part of the thyroid tissue is necrotic, structurally destroyed, cell structure is unclear, and the nucleus disappears; part of the interstitial blood vessels are dilated and congested, and the lumen is enlarged and full; part of the interstitial has inflammatory cells scattered and infiltrated; part of the interstitial fibrous tissue Shows focal or diffuse hyperplasia. (3) Immunohistochemical staining of the NMDA receptor subunit NR2B in thyroid tissue found that NR2B receptor expression was found in each group of thyroid. Membrane and cytoplasm. Measure the average optical density of each group: the normal parent and offspring groups were 122.99±4.17 and 115.17±6.46, respectively, and there was no difference between the two groups; the high fluoride parent group was 169.32±15.21, and the high fluoride progeny group was 94.00±13.33; group F NR2B positive cells were significantly reduced compared with group N, and NR2B positive cells in group f were significantly increased compared with group n. The average optical density between each group was FN/nf (all P 0.01). Conclusion: 1. Excessive exposure to fluoride in parent rats can lead to hypothyroidism and morphological structure damage in offspring rats. 2. Even if the offspring rats leave the high fluoride environment for a long time after birth, the hypothyroidism and morphological structure damage are still difficult to reverse. 3. The above conclusions suggest that in fluorosis areas, it is very important to pay attention to the thyroid function of pregnant women, fetuses and newborns; the thyroid function of fetuses and newborns who are out of high fluoride environment should also arouse our attention. Because it is simple, easy, effective and relatively safe to correct hypothyroidism with substitution therapy, once hypothyroidism is found, TH or thyroid preparations should be used for substitution therapy in time. 4. Immunohistochemical staining found that the rat thyroid had NR2B receptor expression. 5. Excessive exposure to fluoride in parental rats can lead to abnormal expression of thyroid NR2B receptors in the parent and offspring, which may be a manifestation of the excitotoxicity of glutamate. 6. The mechanism by which NR2B receptors cause thyroid damage may constitute an important mechanism for tissue damage caused by fluorosis.
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