目的 探讨左旋甲状腺素(LT4)干预对妊娠期甲状腺功能减退孕大鼠胎盘组织Toll样受体2(TLR2)和TLR4信号通路以及Th1/Th2型免疫应答的影响.方法 取孕Wistar大鼠24只,按体重随机均分为三组:A、B组采用丙基硫氧嘧啶50mg/d灌胃建立甲状腺功能减退模型,B组造模同时采用LT4 0.75mg/kg灌胃;C组作为空白对照.于妊娠第18天,采用放射性免疫法检测各组血清FT4、三碘甲状腺原氨酸(T3)和TSH水平,RT-PCR检测各组胎盘组织TLR2、TLR4、髓样分化因子88(MyD88)、NF-κB mRNA表达,ELISA法检测各组血清IL-6、IL-10、TNF-α含量.结果 与C组比较,A组血清T3、FT4水平降低,TSH水平和胎盘组织TLR2、TLR4、MyD88、NF-κB mRNA表达及血清IL-6、IL-10、TNF-α含量升高(P<0.01).与A组比较,B组血清T3、FT4水平升高,TSH水平和胎盘组织TLR2、TLR4、MyD88、NF-κB mRNA表达及血清IL-6、IL-10、TNF-α含量降低(P<0.01).结论 TLR2和TLR4信号通路活化以及Th1/Th2型免疫应答可能参与了孕大鼠甲状腺功能减退的发病机制,LT4治疗可以通过抑制该通路激活而改善其甲状腺功能.%Objective To investigate the effects of levothyroxine(LT4) on Toll-like receptor 2(TLR2) and TLR4 signaling pathway and Th1/Th2 type immune response in placental tissues of pregnant rats with hypothyroidism.Methods Twenty-four pregnant Wistar rats were randomly divided into three groups with 8 rats each.The rat models with hypothyroidism were established using propylthiouracil 50mg/d by lavage for 18days in groups of A and B.The rats in group B were given LT4 0.75mg/d by lavage at the same time of modeling.Serum levels of free thyroxine(FT4),triiodothyronine(T3) and thyroid stimulating hormone(TSH) were measured by radioimmunoassay on the 18th day of gestation.The mRNA expressions of TLR2,TLR4,myeloblast differentiation factor 88(MyD88) and nuclear transcription factor-κB(NF-κB) were detected by RT-PCR.Serum levels of IL-6,IL-10 and TNF-α were detected by ELISA.Results Compared with group C,serum levels of T3 and FT4 were decreased,TSH and the expressions of TLR2,TLR4,MyD88 and NF-κB mRNA in placental tissues and the levels of IL-6,IL-10,TNF-α in serum were increased in group B(P<0.01).The changes of the indicators above were much less in group B than those in group A(P<0.01).Conclusion The activation of TLR2 and TLR4 signaling pathway and Th1/Th2 immune responses may be involved in the pathogenesis of hypothyroidism in pregnant Wistar rats.LT4 therapy can improve thyroid dysfunction by inhibiting the activation of TLR2 and TLR4 signaling pathway.
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