桥本甲状腺炎对子宫雌激素受体α表达影响

Effect of Hashimoto thyroiditis on estrogen receptor alpha level in the endometrium

目的观察雌激素受体α(ERα)在桥本甲状腺炎(HT)小鼠动情期子宫内膜的表达状况。方法 30只NOD雌性小鼠随机分成正常对照组(CON组)和HT组两组,于HT组小鼠尾根部皮下注射猪甲状腺球蛋白(PTg)制备桥本甲状腺炎鼠模型,通过电化学发光免疫分析法测血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、血清甲状腺球蛋白抗体(Tg Ab)和甲状腺过氧化物酶抗体(TPOAb)水平,ELISA法测定血清促甲状腺激素(TSH)水平;阴道脱落细胞染色选出动情期小鼠;免疫组化法观察两组小鼠动情期子宫内膜ERα表达水平和分布情况;逆转录聚合酶链式反应技术(RTPCR)检测动情期子宫内膜ERαmRNA表达水平;流式液相多重蛋白定量技术(CBA)检测两组小鼠子宫细胞因子白介素(IL)-6和IL-10水平;RT-PCR法检测子宫IL-6和IL-10mRNA表达水平。结果两组T3、T4、TSH差异均无统计学意义,HT组Tg Ab、TPOAb显著高于CON组(P <0. 05),阴道脱落细胞染色显示HT小鼠动情周期各期细胞形态特点与CON组相似;免疫组化法显示ERα在两组小鼠动情期子宫内膜均有表达,免疫组化法和RT-PCR均提示HT组子宫内膜ERα表达水平低于CON组(P <0. 05);RT-PCR和CBA法显示HT组IL-6、IL-10 mRNA和蛋白水平低于CON组(P<0. 05)。结论 HT小鼠存在动情周期,动情期子宫内膜ERα表达水平低,提示HT小鼠能够受孕,但受孕能力可能有所减低。

Objective To observe the expression of estrogen receptor alpha( ERα) in the uterus of Hashimoto thyroiditis( HT). Methods All 30 NOD female mice were divided into two groups randomly,namely,normal control(CON) group and HT group. A mouse model of HT was prepared by subcutaneous injection of pig thyroglobulin.Serum T3,T4,TgAb and TPOAb levels were mesured by electrochemical luminescence immunoassay,and serum TSH were mesured by enzyme-linked immunosorbent( ELISA) assay. Vaginal exfoliative cells were stained to select the estrous mice. Immunohistochemical method was used to observe the expression level and distribution of ERα in both CON group and HT group. The ERα mRNA levels was detected by reverse trancriptase polymerase chain reaction(RT-PCR) in estrus. Cytometric bead array(CBA) method was used to detect the levels of interleukin-6(IL-6)and interleukin-10( IL-10) in the two groups. mRNA expression levels of IL-6 and IL-10 in uterus were detected by RT-PCR. Results The differences of T3,T4 and TSH between the two groups were not statistically significant,and TgAb and TPOAb in HT group were significantly higher than those in the CON group( P < 0. 05). Vaginal exfoliation cell staining showed that the cell morphological characteristics of HT mice were similar to those of the CON group. Immunohistochemistry showed the ERα was expressed in the HT group and the CON group,and both immunohistochemistry and RT-PCR showed the ERα expression level in HT group was lower than that in the CON group(P <0. 05);RT-PCR and CBA showed that IL-6 and IL-10 mRNA and protein levels in the HT group were lower than those in the CON group(P < 0. 05). Conclusion Mice with HT have estrous cycles,and the expression level of ERαin the endometrium is low during the estrous period,suggesting that HT mice can get pregnant but have low fertility.