| ObjectiveTo study the effects of supplying thyroid hormones to low-iodine pregnant rats of different pregnancy on brain development and intelligence in the neonatal rats, explore supplying thyroid hormone during pregnancy,whether can correct the phenomenon of brain development lag caused by thyroid hormone deficiency or not, then find a critical period for treatment.Methods90 1-month-old wistar female rats were randomly divided into 8 groups,we copied the low-iodine model,which made the pregnant rats lack of thyroid hormone.To supply the thyroid hormone to pregnant rats during early or late pregnancy and monitor the level of hormone,then gained the brain tissues of rats in newborn,postneonatal7d(PN7),postneonatal14d(PN14),postneonatal 21d(PN21) and did frozen sections,we researched the ceil apoptosis of the cerebral cortex and hippocampus by TUNEL method,and did statistics on the brain relative quality of different days after offspring birth,then evaluated the learning and memory of 60 days old rats by the water maze.ResultsThe cerebral cortex and hippocampus in normal control group could be seen observed TUNEL-positive cells,the apoptosis index is highest in PN7,and it still maintains a certain number of apoptosis cells in PN14,TUNEL positive cells are very few in PN21,the positive apoptotic cells almost aren't seen in newborn rat brain tissue,the apoptosis peak is delayed of low-iodine group.In the cerebral cortex and hippocampus,the difference of the apoptosis index between the test group in PN7,PN14,PN21 is statistically significant(P＜0.01),but the difference of the apoptosis index of each group in PN1 is no statistical significance(P＞0.05).Each dose group at an early stage,except EL group,the apoptosis index of EM,EH group compare with normal control group in PN7,PN14,PN21,the difference is not statistically significant(P＞0.05),the AI of EL group is higher than the normal control group in the same period(P＜0.05),but lower than the low-iodine group(P＜0.05).The AI of late treatment groups(except the AL group) is lower than the low-iodine group in the same period(P＜0.05),but still higher than the normal control group in the same period(P＜0.05).The difference of the AI between AL Group and low-iodine group is no statistical significance(P＞0.05).The brain relative quality in each group reach a peak in PN7,follow the trend of decline after that,the difference of brain relative quality between the newborn and 7-day-old rats is no statistical significance(P＞0.05), the brain relative quality of each group in PN14,PN21,PN28 is statistically significant(P＜0.01),the difference among AL,EL group and the normal control group is statistically significant in PN14,PN21,PN28(P＜0.05),there is no statistical significance among the rest groups and normal control group(P＞0.05),there is statistical significance among low-iodine group,normal control group and each treatment group(P＜0.05).In the place navigation test,escape latency of rats in each group,there is statistical significance among the first day and the last two days (P＜0.05),the difference among the test groups in the last three days has statistical significance(P＜0.05),after supplying L-T4 to pregnant rats,the latency of offspring shorten significantly,the latency change of EL group is not obvious,compared with low-iodine group's,the difference has no significant difference(P＞0.05).In the spatial probe test,low-iodine rats' swimming time in the platform quadrant,the percentage of swimming path in the objective quadrant account general path,3 ring memory scores compared with the normal group's,the difference has statistically significance(P＜0.01),after L-T4 treatment given,with the exception of EL,AL groups,the three indicators of rest treatment groups compared with normal control group's,there is no statistically significance(P＞0.05),swimming time in the platform quadrant of EL,AL groups are longer than low-iodine group's but shorter than normal control group,the differences both have statistical significance(P＜0.05).the percentage of swimming path in the objective quadrant account general path of EL,AL groups,3 ring memory scores of EL group compared with the low-iodine group's, there was no statistical significance(P＞0.05);The difference of 3 ring memory scores between AL group and low iodine group has statistically significance(P＜0.05). Conclusion1.the cerebral cortex and hippocampus of normal rats appear apoptosis peak at PN7,low-iodine rats not only show apoptosis index increased in brain tissue,but also apoptosis peak is delayed,which hinder the development of brain tissue,and indicate that brain dysfunction caused by low-iodine,the decline of thyroid hormone maybe have relation with the apoptosis of two brain regions.2.After L-T4 replacement therapy given,the apoptosis index of the treatment groups reduced in varying degrees,the effect of early treatment is superior to late treatment,in a certain dose range,and the thyroxine has a good therapeutic effect.3.The brain relative quality of every group rat reached the peak at PN7,the brain relative quality of low-iodine rats increased,after L-T4 replacement therapy,except low-dose group,the brain relative quality of the different treatment groups achieve to normal level.4.The learning and memory ability of low-iodine group rats decline,after L-T4 replacement therapy,with the exception of low-dose group,the learning and memory ability of the different treatment groups' rats reach to the level of normal rats of the same age;low-dose group's learning and memory has not been completely improved, which indicates that have caused some irreversible damage.5.Supplying appropriate L-T4 during early pregnancy can play a necessary role for fetal brain development,so that the fetuses develop normally. |
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