School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Dongfang Hospital of Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Drug Des Devel Ther. 2023 Aug 2;17:2273-2285. doi: 10.2147/DDDT.S410901. eCollection 2023.
Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear.
The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively.
Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group.
Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.
自身免疫性甲状腺炎（AIT）是一种常见的自身免疫性疾病，可导致甲状腺功能障碍。在桥本甲状腺炎患者中，口服薯蓣皂苷后临床症状得到改善。然而，其治疗作用的机制尚不清楚。
在甲状腺球蛋白诱导的自身免疫性甲状腺炎大鼠模型中探索薯蓣皂苷对自身免疫性甲状腺炎的保护作用及潜在机制。首先，通过皮下注射甲状腺球蛋白和饮用碘化钠溶液制备 AIT 大鼠模型，然后灌胃 8 周。麻醉后处死大鼠，保存血清和甲状腺组织样本。采用酶联免疫吸附试验（ELISA）检测血清三碘甲状腺原氨酸（T3）、甲状腺素（T4）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）、甲状腺球蛋白抗体（TgAb）、甲状腺过氧化物酶抗体（TPOAb）和促甲状腺素受体抗体（TRAb）的表达。采用 H&E 染色观察形态学变化。接下来，我们采用转录组学技术寻找薯蓣皂苷的潜在治疗靶点。最后，分别采用逆转录-聚合酶链反应（RT-PCR）和免疫组化（IHC-P）验证转录组学结果。
动物实验结果显示，薯蓣皂苷呈剂量依赖性调节 T3、T4、FT3、TSH、TgAb、TPOAb 和 TRAb，缓解病理过程，其中高剂量组疗效最佳。KEGG 富集分析显示，转录组中核因子 kappa B（NF-κB）通路被鉴定，RT-PCR 和 IHC-P 验证。与 AIT 模型组相比，薯蓣皂苷治疗组 NF-κB、雷帕霉素靶蛋白（mTOR）和 Toll 样受体 4（TLR4）mRNA 和蛋白的相对表达水平降低。
本研究结果表明，薯蓣皂苷治疗可改善 AIT 大鼠的甲状腺功能，下调 TGAb、TPOAb 和 TRAb 水平，可能通过抑制 mTOR 和 TLR4/NF-κB 通路缓解病理过程，抑制炎症反应。
