桥本甲状腺炎对妊娠早期小鼠海马5-羟色胺及受体的影响

Effect of Hashimoto′s thyroiditis on serotonin and receptors in hippocampus of mice during early pregnancy

目的研究桥本甲状腺炎(HT)对妊娠早期小鼠海马组织5-羟色胺(5-HT)含量及5-羟色胺2c受体(5-HT2CR)分布的影响。方法将70只NOD雌性小鼠随机均分为正常怀孕组(CON组)、HT怀孕组(HT组)。通过猪甲状腺球蛋白(pT g)联合弗氏佐剂2次诱导免疫建立HT小鼠模型。随后与雄鼠合笼,妊娠4. 5 d结束,每组随机选取16只孕鼠取材。通过ECLIA、ELISA测定血清甲状腺激素及抗体水平;甲状腺HE染色;ELISA检测各组小鼠海马5-HT含量;Western blot及免疫组织化学法观察各组小鼠海马5-HT2CR含量及分布情况。结果与CON组相比,HT组血清甲状腺过氧化物酶抗体(TPOAb)、抗甲状腺球蛋白抗体(TGAb)水平升高(P <0. 05),游离三碘甲状腺原氨酸(FT3)、游离四碘甲状腺原氨酸(FT4)、促甲状腺激素(TSH)差异无统计学意义;HE染色显示,HT组小鼠较CON组小鼠甲状腺可见部分甲状腺滤泡破坏及淋巴细胞浸润;与CON组相比,HT组小鼠海马5-HT表达水平降低(P <0. 01);与CON组相比,HT组5-HT2CR表达水平升高(P <0. 001),主要分布在海马CA3区锥体细胞层(P <0. 01),CA1和DG区有增高趋势。结论 HT导致妊娠早期小鼠海马5-HT表达降低,5-HT2CR表达增加。

Objective To study the effects of Hashimoto′s thyroiditis(HT)on the content of serotonin(5-HT)and the distribution of serotonin 2 c receptor(5-HT2 CR)in hippocampus of early pregnant mice.Methods 70 NOD female mice were randomly divided into normal pregnancy group(CON group)and HT pregnancy group(HT group).The HT mouse model was established by 2 times induction of immunization with porcine thyroglobulin(pTg)plus Freund′s adjuvant.Then they were caged with male rats and ended at 4.5 d of pregnancy.Each group randomly selected 16 pregnant rats.Serum thyroid hormone and antibody levels were determined by electrochemiluminescence immunoassay(ECLIA)and enzyme-linked ELISA.Thyroid was stained by HE staining.The content of 5-HT in hippocampus of mice in each group was measured by ELISA.The content and distribution of 5-HT2 CR in hippocampus of mice in each group were observed by Western blot and immunohistochemistry.Results Compared with the CON group,the levels of thyroid peroxidase antibody(TPOAb)and anti-thyroglobulin antibody(TGAb)in the HT group increased(P<0.05),and there was no statistically significant difference in free triiodothyronine(FT3),free tetraiodothyronine(FT4)and thyrotrophin(TSH).HE staining showed that some thyroid follicles were destroyed and lymphocytes infiltrated in the thyroid gland of mice in HT group than those in CON mice.The expression of 5-HT in hippocampus of HT group was lower than that of CON group(P<0.01).The expression level of 5-HT2 CR of HT group was higher than that of CON group.The increase(P<0.001)was mainly distributed in the pyramidal cell layer of hippocampal CA3 region(P<0.01),and the CA1 and DG regions showed an increasing trend.Conclusion HT leads to the decrease of 5-HT expression and the increase of 5-HT2 CR expression in hippocampus of early pregnancy mice.