高氟对子代大鼠甲状腺及脑发育、脑功能的影响
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摘要
目的:前期实验中已成功制备出高氟导致甲状腺形态损伤和甲状腺功能低减的亲代模型大鼠。在此基础上,本文进一步观察研究其子代大鼠甲状腺损伤和中枢神经系统脑发育、脑学习记忆功能情况并初步探讨了可能的机制,为治疗和预防高氟导致大脑损伤提供一定的参考。
方法:选用Wistar大鼠36只,雌雄各半,随机分为四组:正常对照组7只、高氟组14只、高氟甲状腺激素替代组7只、单纯甲状腺功能低减组8只,雌雄各半,分别饮用自来水;加入NaF200mg/L/d的高氟水;饮用高氟水的高氟甲状腺激素替代组,一周后同时每天以0.008%甲状腺干制剂混悬液1.8ml/200g体重/只腹腔注射进行替代,并将混悬液浓度每月递增0.008%;甲减组饮用自来水,同时将溶于生理盐水的PTU按lmg/l00g/d腹腔注射。5个月后,各组分别雌雄交配产生子代大鼠,分别为正常子代大鼠(N组):常规喂养;高氟甲状腺功能低减子代大鼠(FP组):此组子代大鼠再随机分为两组,一组为孕后替代组(T2组),饮用高氟水同时,于怀孕后1周起每日腹腔注射甲状腺素(甲状腺片)2μg/l00g体重进行替代,另一组为高氟组(F组),持续饮用高氟水;替代组子代大鼠(T1组):在饮用高氟水同时予甲状腺干制剂混悬液1.8ml/200g体重/只灌胃腹腔注射;单纯甲减子代大鼠(P组):按lmg/l00g/d腹腔注射溶于生理盐水的PTU。30天后子代与母代大鼠分笼,待子代大鼠2-3月龄时,做水迷宫测其脑功能。4月龄时杀鼠,用放射免疫法测定各组子代大鼠血清TT3、TT4、TSH含量;光镜下观察子代大鼠甲状腺和海马形态结构;免疫组化方法检测海马区域NMDAR2B蛋白表达。
结果:
1、生长和体重变化
F组和P组生长曲线明显低于N组(P<0.05),T1组稍高于N组(P>0.05),T2组在10周前与N组相近,10周后体重增长曲线逐渐偏低于N组,但仍高于F和P组(P>0.05)。
2、甲状腺变化
(1)甲状腺指数:F组明显低于N组(P<0.05),而P组明显高于N组(P<0.05),T2组和T1组与N组无差异(P>0.05)。
(2)甲状腺功能:F组和P组TT3、TT4明显低于N组(P<0.05),TSH明显高于N组(P<0.01);T1组TT3、TT4与N组相近(P>0.05),TSH接近正常组(P>0.05);T2组TT3偏低于N组,明显高于F组(P<0.05)和P组,TT4与N组相近(P>0.05),TSH偏高于N组。
(3)HE染色显微镜观察:N组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。滤泡萎缩,滤泡数量减少,排列稀疏,大小不等;间质血管扩张充血,管腔增大,充满;间质有炎细胞散在浸润;间质纤维组织呈灶性或弥漫性增生;P组少量滤泡上皮增生,均见滤泡内胶质减少,滤泡腔空虚,红染均质物减少,间质血管扩张充血,间质血管官腔增大、充满;T1、T2组甲状腺损害较F组和P组轻,仅见滤泡上皮增生。T2组少数可见间质炎细胞浸润和间质血管扩张充血。
3、海马变化
(1)海马指数:P组明显低于N组(P<0.05),F组、T1组和T2组与N组相近(P>0.05)。
(2)水迷宫测定:在第一次水迷宫(学习能力)测试中,F组和P组爬上平台所用时间明显长于N组爬上平台所用时间(P<0.01),T1组和T2组爬上平台所用时间与N组爬上平台所用时间相近(P>0.05)。在第二次水迷宫(记忆能力)测试中,F组和P组爬上平台所用时间明显低于第一次爬上平台所用的时间,但仍然明显长于N组爬上平台所用的时间(P<0.01),T1组和T2组爬上平台所用时间与N组爬上平台所用时间相近(P>0.05)。
(3)HE染色显微镜观察:N组海马神经元细胞排列有序,轮廓清晰,结构和细胞形态正常,细胞核深染,尼氏体清楚可见。F组海马组织结构变疏松,染色变浅,细胞稀疏,有水肿空泡形成。海马神经元细胞肿胀,神经元体积较正常增大,细胞浆染色变浅,胞核体积较正常增大,染色变浅;尼氏体消失;神经元排列明显紊乱,细胞层次结构破坏,极性消失;部分神经纤维增生紊乱,红染丝条状的神经纤维数量增多、增粗、排列;少量神经元坏死,神经元结构模糊或破坏,突起消失,细胞浆染色加深,细胞核结构模糊、固缩、碎裂。P组除了有脑组织水肿及神经元肿胀,神经元变性,神经元排列紊乱外,神经元坏死外,还有胶质细胞增生,脑组织内胶质细胞散在、弥漫、灶性或结节状增生。T1组和T2组海马组织损伤较F组和P组轻,仅见部分脑组织水肿海马神经元轻度肿胀、变性,神经元排列有序,神经元坏死减少。
(4)NMDA受体亚单位NR2B免疫组化染色,数阳性细胞数:NMDAR2B受体免疫组化染色呈棕黄色,主要着色在海马CA1区的胞膜及胞浆,胞核不着色。F组和P组阳性细胞比值明显少于N组(P<0.01),T1组阳性细胞比值与N组相近(P>0.05),T2组阳性细胞比值高于F组,明显高于P组(P<0.05)。
4、大脑变化
大脑重量:F组和P组大脑重量偏低于N组(P<0.05),T1组、T2组大脑重量于N组相近(P>0.05)。各组大脑指数无明显差异。
结论:
1、慢性氟中毒子代大鼠与亲代大鼠一样可发生明显的脑损伤和脑认知能力降低。
2、慢性氟中毒子代大鼠与亲代大鼠一样可发生明显的甲状腺损伤和甲状腺功能降低。
3、慢性氟中毒子代大鼠,无论是在氟中毒同时防止甲状腺功能低减还是在其胚胎期纠正甲状腺功能低减,均可明显减轻脑损伤和脑认知能力降低。强烈提示,慢性氟中毒子代大鼠高氟作用下甲状腺功能低减是导致其脑损伤、脑功能障碍的另一重要病机。
4、考虑到胎儿、婴幼儿的脑发育特点和重要性,在氟中毒防治工作中,纠正慢性氟中毒地区胎儿和婴幼儿甲状腺功能低减尤为重要。
5、海马NBMDAR_2B受体数量的减少,可能是高氟子代大鼠发生脑损伤和脑认知能力降低的一个重要机制。
Objective:The parent rats, including the rats with thyroid function reduced and the rats with thyroid form damaged caused by high fluorine, have been prepared successfully in the former experiments. Based on this, the influence of high fluorine to the offspring rats is researched in this paper. The mechanism, specifically means how high fluorine causes the thyroid damage, then effects the growth and the learning ability of the central nervous system brain, is focused through the experiment. The study of the mechanism can provide some reference for the remedy and prevention of the brain damage caused by high fluorine.
Methods:Selected Wistar rats were 36, were randomly divided into four groups: normal control group, seven, high-dose group 14, high fluoride thyroid hormone replacement group of seven, simple thyroid function low-cut group of eight male and female half and half were drinking tap water; join NaF200mg/L/d of high fluoride water; drink high fluoride water fluoride thyroid hormone replacement group, at the same time every week to 0.008% dry preparation suspension 1.8ml/200g thyroid weight only be replaced by intraperitoneal injection, and suspension concentration of 0.008% per month increase; hypothyroidism drinking water, while PTU dissolved in saline by intraperitoneal injection lmg/l00g/d. Each group after 5 months in each group were divided male and female mating produces offspring rats were offspring of normal rats (N group); fluoride hypothyroidism offspring rats (FP group): fluoride hypothyroidism child on behalf of the rats were randomly divided into two groups, one group after pregnancy substitution group (T2 group), drinking high fluoride water at the same time, the pregnancy after 1 week of daily intraperitoneal injection of thyroxine (thyroid tablets) 2μg/l00g weight 25 days to replace, the other group was high-dose group (F group), continued to drink high fluoride water; alternative group offspring rats (T1 group): fluoride in drinking water at the same time to dry preparations of thyroid suspension 1.8ml/200g body weight only administered intraperitoneally; simple hypothyroidism offspring rats (P): According to lmg/l00g/d intraperitoneal injection of normal saline in the PTU. 30 days after the offspring and the mother on behalf of the rats were divided into the cage, offspring rats were fed the same manner as with the parent until the offspring rats 4 months old, to kill rats. Measured by radioimmunoassay offspring of each group serum TT3, TT4, TSH levels; light microscope thyroid and hippocampus in rat offspring morphology; immunohistochemistry to detect protein expression in hippocampus region NMDAR2B.
Results:
1、Growth and body weight changes:in F group and P group were significantly lower than the growth curve of N group (P <0.05), T1 group slightly higher than the N group (P> 0.05), T2 group and the N group before 10 weeks, similar to 10 weeks low body weight gradually after the growth curve in the N group, but still high in F and P group (P> 0.05).
2、Thyroid changes
(1)Thyroid Index: F group was lower than N group (P <0.05), while the P group was significantly higher than N group (P <0.05), T2 and T1 group and N group was no difference (P> 0.05).
(2)thyroid function: F group and P group TT3, TT4 significantly lower than the N group (P <0.05), TSH was significantly higher than N group (P <0.01); T1 group TT3, TT4 and N group similar (P> 0.05 ), TSH close to the normal group (P> 0.05); T2 group TT3 lower than the N group, significantly higher than the F group (P <0.05) and P group, TT4 and N group similar (P> 0.05), TSH high in N group.
(3)HE staining microscope: N group of normal thyroid follicular structure, arranged in order, follicular non-proliferation or atrophy; F Group follicular epithelial hyperplasia, increased number and level, disorganized, and cells were columnar or high columnar, or even to highlight the formation of follicular cavities nipple. Follicles shrink, reducing the number of follicles, arranged in sparse sizes; stromal vascular dilatation and congestion, lumen, filled; stromal infiltration of inflammatory cells scattered; interstitial fibrosis was focal or diffuse hyperplasia; P group a small amount of follicular epithelial hyperplasia, were observed within the colloid follicles reduced follicular cavity empty, red staining homogeneous material reduction in stromal vascular dilatation and congestion, increased stromal vascular bureaucratic, full of; T1, T2 group compared with thyroid damage F group and P group light, seen in follicular epithelial hyperplasia. T2 visible minority group interstitial infiltration of inflammatory cells and interstitial vascular congestion expansion.
3、Hippocampal changes
(1)Hippocampus Index: P group was lower than N group (P <0.05), F group, T1 and T2 group and N group group similar (P> 0.05).
(2)Determination of the water maze: the first water maze (learning capacity) test, F group and P group climbed the platform significantly longer than those used in N group climbed the platform, time spent (P <0.01), T1 and T2 group climbing group time spent on the platform, climb up the platform with the N group with time similar (P> 0.05). A second water maze (memory) test, F group and P group climbed platform was significantly lower than time spent climbing platform, the first time used, but still significantly longer than the N group climb the platform on the time (P < 0.01), T1 and T2 group climbed the platform group by using time and climb up the platform with the N group of the time similar (P> 0.05).
(3)HE stain microscopy: N hippocampal neurons arranged in order, a clear outline, structure and normal cell morphology, cell nucleus stained Nissl bodies visible. F loose change in hippocampal structure, dyeing lighter, cell sparse, edema vacuolation. Hippocampal neurons in cell swelling, increased neuronal size than normal, lighter staining cytoplasm, nucleus volume increase than normal, lighter staining; Nissl bodies disappear; neurons arranged in apparent disorder, the cell-level structural damage, polarity disappeared; part of the nerve fiber proliferation disorders, red dyed silk strips increase in the number of nerve fibers, thickening, arrangement; a small amount of neuronal death, neuron structure, fuzzy or destruction processes disappear, deeper staining cytoplasm, nucleus and confused, condensation , fragmentation. P group in addition to brain edema and neuronal swelling and degeneration of neurons, neurons disordered, the neuronal death, there is proliferation of glial cells, glial cells within the brain tissue scattered, diffuse, focal or nodular hyperplasia. T1 and T2 group than in hippocampal tissue injury group and P group F light, only see part of the hippocampal neurons of brain edema with mild swelling, degeneration of neurons arranged in order, reduce neuronal death.
(4)NMDA receptor subunit NR2B immunohistochemistry, the number of positive cells: NMDAR2B receptor immunohistochemical staining was brown, the main color in the hippocampal CA1 area of the membrane and cytoplasm, the nucleus was not stained. F group and N group cells similar (P> 0.05), T1 and T2 group than the N group of cells a few cells high (P> 0.05), P group cells was significantly higher than the N group (P <0.05); F Groups of cells were significantly less than the N group (P <0.05), T1, T2 group and P group positive cells and the N group close to (P> 0.05); each group the ratio of positive cells compared to total cells: F group and P The positive cells were significantly less than the N group (P <0.01), T1 group and N group the ratio of positive cells similar (P> 0.05).
4、Changes in the brain
Brain weight: F group and P group brain weight low in the N group (P <0.05), T1 group, T2 group similar brain weight in the N group (P> 0.05). Index in each group no significant difference in the brain.
Conclusion:
1、Rat offspring of chronic fluorosis in rats with the same parent can cause the obvious brain damage and brain cognitive ability.
2、Offspring rats with chronic fluorosis in rats with the same parent can cause the obvious decrease of thyroid damage and thyroid function.
3、Offspring rats with chronic fluorosis, fluorosis, whether in low thyroid function and also to prevent or reduce the period of their embryos by correcting low thyroid function, can significantly reduce brain damage and brain cognitive ability. So strongly suggest that chronic fluorine poisoning fluorine under the action of rat offspring of low thyroid function is reduced leading to brain damage, brain dysfunction, another important pathogenesis.
4、Taking into account the fetus, infant brain development characteristics and importance of prevention work, to correct chronic fluorine poisoning area fetuses and infants with low thyroid function less important.
5、Reducing the number of hippocampal NBMDAR_2B receptors may be occurring fluoride in rat offspring brain damage and cerebral lower cognitive ability is an important mechanism.
方法:选用Wistar大鼠36只,雌雄各半,随机分为四组:正常对照组7只、高氟组14只、高氟甲状腺激素替代组7只、单纯甲状腺功能低减组8只,雌雄各半,分别饮用自来水;加入NaF200mg/L/d的高氟水;饮用高氟水的高氟甲状腺激素替代组,一周后同时每天以0.008%甲状腺干制剂混悬液1.8ml/200g体重/只腹腔注射进行替代,并将混悬液浓度每月递增0.008%;甲减组饮用自来水,同时将溶于生理盐水的PTU按lmg/l00g/d腹腔注射。5个月后,各组分别雌雄交配产生子代大鼠,分别为正常子代大鼠(N组):常规喂养;高氟甲状腺功能低减子代大鼠(FP组):此组子代大鼠再随机分为两组,一组为孕后替代组(T2组),饮用高氟水同时,于怀孕后1周起每日腹腔注射甲状腺素(甲状腺片)2μg/l00g体重进行替代,另一组为高氟组(F组),持续饮用高氟水;替代组子代大鼠(T1组):在饮用高氟水同时予甲状腺干制剂混悬液1.8ml/200g体重/只灌胃腹腔注射;单纯甲减子代大鼠(P组):按lmg/l00g/d腹腔注射溶于生理盐水的PTU。30天后子代与母代大鼠分笼,待子代大鼠2-3月龄时,做水迷宫测其脑功能。4月龄时杀鼠,用放射免疫法测定各组子代大鼠血清TT3、TT4、TSH含量;光镜下观察子代大鼠甲状腺和海马形态结构;免疫组化方法检测海马区域NMDAR2B蛋白表达。
结果:
1、生长和体重变化
F组和P组生长曲线明显低于N组(P<0.05),T1组稍高于N组(P>0.05),T2组在10周前与N组相近,10周后体重增长曲线逐渐偏低于N组,但仍高于F和P组(P>0.05)。
2、甲状腺变化
(1)甲状腺指数:F组明显低于N组(P<0.05),而P组明显高于N组(P<0.05),T2组和T1组与N组无差异(P>0.05)。
(2)甲状腺功能:F组和P组TT3、TT4明显低于N组(P<0.05),TSH明显高于N组(P<0.01);T1组TT3、TT4与N组相近(P>0.05),TSH接近正常组(P>0.05);T2组TT3偏低于N组,明显高于F组(P<0.05)和P组,TT4与N组相近(P>0.05),TSH偏高于N组。
(3)HE染色显微镜观察:N组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。滤泡萎缩,滤泡数量减少,排列稀疏,大小不等;间质血管扩张充血,管腔增大,充满;间质有炎细胞散在浸润;间质纤维组织呈灶性或弥漫性增生;P组少量滤泡上皮增生,均见滤泡内胶质减少,滤泡腔空虚,红染均质物减少,间质血管扩张充血,间质血管官腔增大、充满;T1、T2组甲状腺损害较F组和P组轻,仅见滤泡上皮增生。T2组少数可见间质炎细胞浸润和间质血管扩张充血。
3、海马变化
(1)海马指数:P组明显低于N组(P<0.05),F组、T1组和T2组与N组相近(P>0.05)。
(2)水迷宫测定:在第一次水迷宫(学习能力)测试中,F组和P组爬上平台所用时间明显长于N组爬上平台所用时间(P<0.01),T1组和T2组爬上平台所用时间与N组爬上平台所用时间相近(P>0.05)。在第二次水迷宫(记忆能力)测试中,F组和P组爬上平台所用时间明显低于第一次爬上平台所用的时间,但仍然明显长于N组爬上平台所用的时间(P<0.01),T1组和T2组爬上平台所用时间与N组爬上平台所用时间相近(P>0.05)。
(3)HE染色显微镜观察:N组海马神经元细胞排列有序,轮廓清晰,结构和细胞形态正常,细胞核深染,尼氏体清楚可见。F组海马组织结构变疏松,染色变浅,细胞稀疏,有水肿空泡形成。海马神经元细胞肿胀,神经元体积较正常增大,细胞浆染色变浅,胞核体积较正常增大,染色变浅;尼氏体消失;神经元排列明显紊乱,细胞层次结构破坏,极性消失;部分神经纤维增生紊乱,红染丝条状的神经纤维数量增多、增粗、排列;少量神经元坏死,神经元结构模糊或破坏,突起消失,细胞浆染色加深,细胞核结构模糊、固缩、碎裂。P组除了有脑组织水肿及神经元肿胀,神经元变性,神经元排列紊乱外,神经元坏死外,还有胶质细胞增生,脑组织内胶质细胞散在、弥漫、灶性或结节状增生。T1组和T2组海马组织损伤较F组和P组轻,仅见部分脑组织水肿海马神经元轻度肿胀、变性,神经元排列有序,神经元坏死减少。
(4)NMDA受体亚单位NR2B免疫组化染色,数阳性细胞数:NMDAR2B受体免疫组化染色呈棕黄色,主要着色在海马CA1区的胞膜及胞浆,胞核不着色。F组和P组阳性细胞比值明显少于N组(P<0.01),T1组阳性细胞比值与N组相近(P>0.05),T2组阳性细胞比值高于F组,明显高于P组(P<0.05)。
4、大脑变化
大脑重量:F组和P组大脑重量偏低于N组(P<0.05),T1组、T2组大脑重量于N组相近(P>0.05)。各组大脑指数无明显差异。
结论:
1、慢性氟中毒子代大鼠与亲代大鼠一样可发生明显的脑损伤和脑认知能力降低。
2、慢性氟中毒子代大鼠与亲代大鼠一样可发生明显的甲状腺损伤和甲状腺功能降低。
3、慢性氟中毒子代大鼠,无论是在氟中毒同时防止甲状腺功能低减还是在其胚胎期纠正甲状腺功能低减,均可明显减轻脑损伤和脑认知能力降低。强烈提示,慢性氟中毒子代大鼠高氟作用下甲状腺功能低减是导致其脑损伤、脑功能障碍的另一重要病机。
4、考虑到胎儿、婴幼儿的脑发育特点和重要性,在氟中毒防治工作中,纠正慢性氟中毒地区胎儿和婴幼儿甲状腺功能低减尤为重要。
5、海马NBMDAR_2B受体数量的减少,可能是高氟子代大鼠发生脑损伤和脑认知能力降低的一个重要机制。
Objective:The parent rats, including the rats with thyroid function reduced and the rats with thyroid form damaged caused by high fluorine, have been prepared successfully in the former experiments. Based on this, the influence of high fluorine to the offspring rats is researched in this paper. The mechanism, specifically means how high fluorine causes the thyroid damage, then effects the growth and the learning ability of the central nervous system brain, is focused through the experiment. The study of the mechanism can provide some reference for the remedy and prevention of the brain damage caused by high fluorine.
Methods:Selected Wistar rats were 36, were randomly divided into four groups: normal control group, seven, high-dose group 14, high fluoride thyroid hormone replacement group of seven, simple thyroid function low-cut group of eight male and female half and half were drinking tap water; join NaF200mg/L/d of high fluoride water; drink high fluoride water fluoride thyroid hormone replacement group, at the same time every week to 0.008% dry preparation suspension 1.8ml/200g thyroid weight only be replaced by intraperitoneal injection, and suspension concentration of 0.008% per month increase; hypothyroidism drinking water, while PTU dissolved in saline by intraperitoneal injection lmg/l00g/d. Each group after 5 months in each group were divided male and female mating produces offspring rats were offspring of normal rats (N group); fluoride hypothyroidism offspring rats (FP group): fluoride hypothyroidism child on behalf of the rats were randomly divided into two groups, one group after pregnancy substitution group (T2 group), drinking high fluoride water at the same time, the pregnancy after 1 week of daily intraperitoneal injection of thyroxine (thyroid tablets) 2μg/l00g weight 25 days to replace, the other group was high-dose group (F group), continued to drink high fluoride water; alternative group offspring rats (T1 group): fluoride in drinking water at the same time to dry preparations of thyroid suspension 1.8ml/200g body weight only administered intraperitoneally; simple hypothyroidism offspring rats (P): According to lmg/l00g/d intraperitoneal injection of normal saline in the PTU. 30 days after the offspring and the mother on behalf of the rats were divided into the cage, offspring rats were fed the same manner as with the parent until the offspring rats 4 months old, to kill rats. Measured by radioimmunoassay offspring of each group serum TT3, TT4, TSH levels; light microscope thyroid and hippocampus in rat offspring morphology; immunohistochemistry to detect protein expression in hippocampus region NMDAR2B.
Results:
1、Growth and body weight changes:in F group and P group were significantly lower than the growth curve of N group (P <0.05), T1 group slightly higher than the N group (P> 0.05), T2 group and the N group before 10 weeks, similar to 10 weeks low body weight gradually after the growth curve in the N group, but still high in F and P group (P> 0.05).
2、Thyroid changes
(1)Thyroid Index: F group was lower than N group (P <0.05), while the P group was significantly higher than N group (P <0.05), T2 and T1 group and N group was no difference (P> 0.05).
(2)thyroid function: F group and P group TT3, TT4 significantly lower than the N group (P <0.05), TSH was significantly higher than N group (P <0.01); T1 group TT3, TT4 and N group similar (P> 0.05 ), TSH close to the normal group (P> 0.05); T2 group TT3 lower than the N group, significantly higher than the F group (P <0.05) and P group, TT4 and N group similar (P> 0.05), TSH high in N group.
(3)HE staining microscope: N group of normal thyroid follicular structure, arranged in order, follicular non-proliferation or atrophy; F Group follicular epithelial hyperplasia, increased number and level, disorganized, and cells were columnar or high columnar, or even to highlight the formation of follicular cavities nipple. Follicles shrink, reducing the number of follicles, arranged in sparse sizes; stromal vascular dilatation and congestion, lumen, filled; stromal infiltration of inflammatory cells scattered; interstitial fibrosis was focal or diffuse hyperplasia; P group a small amount of follicular epithelial hyperplasia, were observed within the colloid follicles reduced follicular cavity empty, red staining homogeneous material reduction in stromal vascular dilatation and congestion, increased stromal vascular bureaucratic, full of; T1, T2 group compared with thyroid damage F group and P group light, seen in follicular epithelial hyperplasia. T2 visible minority group interstitial infiltration of inflammatory cells and interstitial vascular congestion expansion.
3、Hippocampal changes
(1)Hippocampus Index: P group was lower than N group (P <0.05), F group, T1 and T2 group and N group group similar (P> 0.05).
(2)Determination of the water maze: the first water maze (learning capacity) test, F group and P group climbed the platform significantly longer than those used in N group climbed the platform, time spent (P <0.01), T1 and T2 group climbing group time spent on the platform, climb up the platform with the N group with time similar (P> 0.05). A second water maze (memory) test, F group and P group climbed platform was significantly lower than time spent climbing platform, the first time used, but still significantly longer than the N group climb the platform on the time (P < 0.01), T1 and T2 group climbed the platform group by using time and climb up the platform with the N group of the time similar (P> 0.05).
(3)HE stain microscopy: N hippocampal neurons arranged in order, a clear outline, structure and normal cell morphology, cell nucleus stained Nissl bodies visible. F loose change in hippocampal structure, dyeing lighter, cell sparse, edema vacuolation. Hippocampal neurons in cell swelling, increased neuronal size than normal, lighter staining cytoplasm, nucleus volume increase than normal, lighter staining; Nissl bodies disappear; neurons arranged in apparent disorder, the cell-level structural damage, polarity disappeared; part of the nerve fiber proliferation disorders, red dyed silk strips increase in the number of nerve fibers, thickening, arrangement; a small amount of neuronal death, neuron structure, fuzzy or destruction processes disappear, deeper staining cytoplasm, nucleus and confused, condensation , fragmentation. P group in addition to brain edema and neuronal swelling and degeneration of neurons, neurons disordered, the neuronal death, there is proliferation of glial cells, glial cells within the brain tissue scattered, diffuse, focal or nodular hyperplasia. T1 and T2 group than in hippocampal tissue injury group and P group F light, only see part of the hippocampal neurons of brain edema with mild swelling, degeneration of neurons arranged in order, reduce neuronal death.
(4)NMDA receptor subunit NR2B immunohistochemistry, the number of positive cells: NMDAR2B receptor immunohistochemical staining was brown, the main color in the hippocampal CA1 area of the membrane and cytoplasm, the nucleus was not stained. F group and N group cells similar (P> 0.05), T1 and T2 group than the N group of cells a few cells high (P> 0.05), P group cells was significantly higher than the N group (P <0.05); F Groups of cells were significantly less than the N group (P <0.05), T1, T2 group and P group positive cells and the N group close to (P> 0.05); each group the ratio of positive cells compared to total cells: F group and P The positive cells were significantly less than the N group (P <0.01), T1 group and N group the ratio of positive cells similar (P> 0.05).
4、Changes in the brain
Brain weight: F group and P group brain weight low in the N group (P <0.05), T1 group, T2 group similar brain weight in the N group (P> 0.05). Index in each group no significant difference in the brain.
Conclusion:
1、Rat offspring of chronic fluorosis in rats with the same parent can cause the obvious brain damage and brain cognitive ability.
2、Offspring rats with chronic fluorosis in rats with the same parent can cause the obvious decrease of thyroid damage and thyroid function.
3、Offspring rats with chronic fluorosis, fluorosis, whether in low thyroid function and also to prevent or reduce the period of their embryos by correcting low thyroid function, can significantly reduce brain damage and brain cognitive ability. So strongly suggest that chronic fluorine poisoning fluorine under the action of rat offspring of low thyroid function is reduced leading to brain damage, brain dysfunction, another important pathogenesis.
4、Taking into account the fetus, infant brain development characteristics and importance of prevention work, to correct chronic fluorine poisoning area fetuses and infants with low thyroid function less important.
5、Reducing the number of hippocampal NBMDAR_2B receptors may be occurring fluoride in rat offspring brain damage and cerebral lower cognitive ability is an important mechanism.
引文
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