| 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 brainBrain 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 NBMDAR2B receptors may be occurring fluoride in rat offspring brain damage and cerebral lower cognitive ability is an important mechanism. |
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