LT_4干预对甲状腺功能减退孕大鼠胎盘组织TLR2和TLR4表达以及Th1/Th2型免疫应答的影响  

Effects of LT_4 on the expressions of TLR2 and TLR4 and Th1/Th2 type immune response in placental tissues of pregnant rats with hypothyroidism

作　　者：张爱华[1] 郦培昕 张玉仙[1] ZHANG Aihua LI Peixin ZHANG Yuxian(Department of Gynaecology and Obstetrics, Affiliated Danyang People＇s Hospital, Nantong University, Danyang 212300, CHINA)

机构地区：[1]南通大学附属丹阳市人民医院妇产科,江苏省丹阳市212300

出　　处：《江苏医药》2017年第17期1213-1216,共4页Jiangsu Medical Journal

摘　　要：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（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 8rats each.The rat models with hypothyroidism were established using propylthiouracil 50mg/d by lavage for 18 days in groups of A and B.The rats in group B were given LT40.75 mg/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 18 th 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-αwere 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-αin 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 TLR4signaling 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 TLR4signaling pathway.

关 键 词：甲状腺功能减退 妊娠 左旋甲状腺素 TOLL样受体 免疫应答 

分 类 号：R714[医药卫生—妇产科学]