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目的探讨妊娠大鼠甲状腺功能减退对仔鼠海马络丝蛋白(RELN)和脑源性神经营养因子(BDNF)表达的影响。方法采用放射免疫法测定妊娠第15天对照组、甲状腺功能减退组、甲状腺功能减退孕期治疗组和甲状腺功能减退产后治疗组4组,每组7只孕鼠的血清中甲状腺激素水平。采用免疫组织化学方法分析对照组、甲状腺功能减退组、甲状腺功能减退孕期治疗组和甲状腺功能减退产后治疗组,每组6只仔鼠海马CA1区RELN和BDNF蛋白的表达。结果 1妊娠第15天甲状腺功能减退组、甲状腺功能减退孕期治疗组和甲状腺功能减退产后治疗组3组母鼠血清中总甲状腺素(TT4)水平明显低于对照组(P<0.05),促甲状腺激素(TSH)水平明显高于对照组(P<0.05);2甲状腺功能减退组、甲状腺功能减退产后治疗组仔鼠海马RELN和BDNF蛋白表达明显低于对照组,差异均有统计学意义(P<0.05)。3甲状腺功能减退组、甲状腺功能减退产后治疗组仔鼠海马RELN和BDNF蛋白表达明显低于甲状腺功能减退孕期治疗组,差异均有统计学意义(P<0.05)。结论甲状腺功能减退的孕期治疗RELN和BDNF蛋白表达改变不明显,但产后治疗RELN和BDNF蛋白表达降低,影响子代脑发育。孕期补充甲状腺激素治疗甲状腺功能减退组对减轻子代脑发育异常有益,在临床上为预防及治疗甲状腺功能减退组所致的胎儿脑发育异常提供新的理论依据。
Objective To investigate the effect of hypothyroidism in pregnancy on the expression of hippocampal filaggrin (RELN) and brain-derived neurotrophic factor (BDNF) in offspring rats. Methods Serum levels of thyroid hormones in the control group, hypothyroidism group, hypothyroidism pregnancy group and hypothyroidism postpartum treatment group 4 were measured by radioimmunoassay. Immunohistochemistry was used to analyze the expression of RELN and BDNF in the hippocampal CA1 region of 6 neonates in the control group, hypothyroidism group, hypothyroidism pregnancy group and hypothyroidism postnatal treatment group. Results The level of serum total thyroxine (TT4) in the three groups of maternal serum of hypothyroidism group, hypothyroidism group and hypothyroidism postnatal treatment group on the 15th day of gestation was significantly lower than that of the control group (P <0.05) (P <0.05). The levels of RELN and BDNF protein in the hippocampus in the hypothyroidism group and the hypothyroidism group were significantly lower than those in the control group (P <0.05). The differences were statistically significant (P <0.05). 3 Hypothyroidism group, hypothyroidism postnatal treatment group offspring hippocampus RELN and BDNF protein expression was significantly lower than the hypothyroidism treatment group during pregnancy, the difference was statistically significant (P <0.05). Conclusion The expression of RELN and BDNF in pregnant women with hypothyroidism did not change obviously during the pregnancy, but the expression of RELN and BDNF in postpartum treatment decreased, which affected the brain development of offspring. Thyroid hormone replacement therapy during pregnancy hypothyroidism group to reduce offspring of brain dysplasia benefit, in clinical prevention and treatment of hypothyroidism caused by fetal brain development abnormalities provide a new theoretical basis.