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香豆雌酚通过调节实验性自身免疫性甲状腺炎中的Th1反应来抑制自身抗体的产生。

Coumestrol inhibits autoantibody production through modulating Th1 response in experimental autoimmune thyroiditis.

作者信息

Jin Xiaojing, Wang Shujun, Zhao Xuemin, Jin Qian, Fan Chenling, Li Jing, Shan Zhongyan, Teng Weiping

机构信息

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Affiliated Hospital, China Medical University, Liaoning Provincial Key Laboratory of Endocrine Diseases, Shenyang, P. R. China.

Present address: Department of Emergency, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, P.R. China.

出版信息

Oncotarget. 2016 Aug 16;7(33):52797-52809. doi: 10.18632/oncotarget.10353.

Abstract

Coumestrol is a common phytoestrogen found in plants and Chinese medicinal herbs. Its influences on experimental autoimmune thyroiditis (EAT) were investigated in this study. Female adult CBA/J mice were fed with drinking water containing 1% Tween80 only (Control group), 0.8 mg/l (L group) and 8 mg/l coumestrol (H group) from 6 to 15 weeks of age, respectively. Their serum coumestrol concentrations were determined by high performance liquid chromatography, which were undetectable, 43.70 ± 21.74 ng/ml and 135.07 ± 70.40 ng/ml, respectively. In addition, the mice (n = 14-16/group) were immunized twice with thyroglobulin (Tg) and Freund's adjuvant to induce EAT during the meantime. Although no overt changes in the extent of intrathyroidal mononuclear cell infiltration were shown in the two coumestrol-treated groups as compared with the controls, serum anti-Tg IgG2a, IgG3 and IgG1 titers, ratio of IgG2a to IgG1 and the percentage of T helper (Th)1 cells in the splenocytes were significantly reduced in the L group. Another consistent change was the significantly decreased expression of splenic IFN-γ mRNA after low dose of coumestrol exposure. Uterine weight was also markedly reduced in the mice of L group. These findings suggest that coumestrol treatment may have some beneficial actions against thyroid-specific autoantibody production in the development of autoimmune thyroiditis through suppression of Th1 response due to its anti-estrogenic activity.

摘要

香豆雌酚是一种常见于植物和中草药中的植物雌激素。本研究调查了其对实验性自身免疫性甲状腺炎(EAT)的影响。雌性成年CBA/J小鼠在6至15周龄时分别饮用仅含1%吐温80的饮用水(对照组)、0.8毫克/升香豆雌酚的饮用水(低剂量组)和8毫克/升香豆雌酚的饮用水(高剂量组)。通过高效液相色谱法测定它们的血清香豆雌酚浓度,结果分别为未检测到、43.70±21.74纳克/毫升和135.07±70.40纳克/毫升。此外,在此期间,每组14 - 16只小鼠用甲状腺球蛋白(Tg)和弗氏佐剂免疫两次以诱导EAT。虽然与对照组相比,两个香豆雌酚处理组的甲状腺内单核细胞浸润程度没有明显变化,但低剂量组的血清抗Tg IgG2a、IgG3和IgG1滴度、IgG2a与IgG1的比值以及脾细胞中辅助性T细胞(Th)1的百分比均显著降低。另一个一致的变化是低剂量香豆雌酚暴露后脾脏IFN-γ mRNA的表达显著降低。低剂量组小鼠的子宫重量也明显减轻。这些发现表明,香豆雌酚治疗可能通过其抗雌激素活性抑制Th1反应,从而在自身免疫性甲状腺炎的发展过程中对甲状腺特异性自身抗体的产生具有一些有益作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbbb/5288149/be5f3e2c2ad9/oncotarget-07-52797-g001.jpg

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