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薯蓣皂素对大鼠自身免疫性甲状腺炎作用的转录组学分析。

Transcriptome analysis of the effect of diosgenin on autoimmune thyroiditis in a rat model.

机构信息

Dongfang Hospital of Beijing University of Chinese Medicine, Beijing, China.

Technology Department, Beijing University of Chinese Medicine, Beijing, China.

出版信息

Sci Rep. 2021 Mar 18;11(1):6401. doi: 10.1038/s41598-021-85822-1.

Abstract

In a mouse model of Graves' disease (GD), diosgenin has been shown to have a therapeutic effect on GD by alleviating goitre. However, research on the effect of diosgenin on autoimmune thyroiditis (AIT) is lacking. In this study, transcriptomics was used to comprehensively analyse the protective effect of diosgenin against AIT in rats and the possible mechanism. The results showed that in the diosgenin-intervention group, compared to the model group, the expression of serum triiodothyronine, thyroxine, free triiodothyronine, and free thyroxine was decreased and that of thyroid-stimulating hormone was increased; these changes were accompanied by the downregulation of thyroglobulin, TSH receptor antibody and thyroid peroxidase expression in serum. Furthermore, transcriptome detection, RT-qPCR and immunohistochemistry verification revealed that in thyroid tissue, the relative mRNA and protein expression of cyclic adenosine 3',5'-monophosphate (cAMP), protein kinase A (PKA) and cAMP response element-binding protein (Creb) were increased and the mRNA expression of S100 calcium-binding protein A9 (S100A9) was decreased in the diosgenin groups. In summary, diosgenin alleviates the development of AIT, possibly via the activation of the cAMP/PKA/Creb pathway and downregulation of S100A9 gene expression.

摘要

在格雷夫斯病(GD)的小鼠模型中,薯蓣皂苷元已被证明通过缓解甲状腺肿对 GD 具有治疗作用。然而,关于薯蓣皂苷元对自身免疫性甲状腺炎(AIT)的作用的研究还很少。在这项研究中,转录组学被用来全面分析薯蓣皂苷元对大鼠 AIT 的保护作用及其可能的机制。结果表明,与模型组相比,薯蓣皂苷元干预组血清三碘甲状腺原氨酸、甲状腺素、游离三碘甲状腺原氨酸和游离甲状腺素的表达降低,促甲状腺激素的表达增加;这些变化伴随着血清中甲状腺球蛋白、促甲状腺激素受体抗体和甲状腺过氧化物酶表达的下调。此外,转录组检测、RT-qPCR 和免疫组织化学验证表明,在甲状腺组织中,薯蓣皂苷元组 cAMP、蛋白激酶 A(PKA)和 cAMP 反应元件结合蛋白(Creb)的相对 mRNA 和蛋白表达增加,S100 钙结合蛋白 A9(S100A9)的 mRNA 表达降低。总之,薯蓣皂苷元缓解 AIT 的发展,可能是通过激活 cAMP/PKA/Creb 通路和下调 S100A9 基因表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0a/7973441/4199686d9596/41598_2021_85822_Fig1_HTML.jpg

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