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目的探讨左旋甲状腺素(LT_4)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LT_4 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FT_4、三碘甲状腺原氨酸(T_3)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T_3、FT_4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T_3、FT_4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,LT_4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 (LT_4) intervention on Toll-like receptor 2 (TLR2), TLR4 signaling pathway and Th1 / Th2 immune response in placenta of pregnant rats with hypothyroidism. Methods Twenty-four pregnant Wistar rats were randomly divided into three groups according to their body weight. Groups A and B were given 50 mg / d propylthiouracil to establish hypothyroidism model. Group B was given LT 0.75 mg / kg Gavage; C group as a blank control. On the 18th day of gestation, the levels of FT_4, triiodothyronine (T_3) and TSH in each group were detected by radioimmunoassay. The placental TLR2, TLR4, myD88, The expression of NF-κB mRNA and IL-6, IL-10 and TNF-α in each group were detected by ELISA. Results Compared with group C, the levels of serum T_3 and FT_4 in group A were decreased, the levels of TSH and the expressions of TLR2, TLR4, MyD88 and NF-κB in placenta and the levels of IL-6, IL-10 and TNF- 0.01). Compared with group A, the levels of serum T_3 and FT_4 in serum of group B were increased, the levels of TSH and the expressions of TLR2, TLR4, MyD88 and NF-κB mRNA and the levels of IL-6, IL-10 and TNF- ). Conclusion Activation of TLR2 and TLR4 signaling pathway and Th1 / Th2 immune response may be involved in the pathogenesis of hypothyroidism in pregnant rats. LT_4 treatment may improve thyroid function by inhibiting the activation of this pathway.