Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease
Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease
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DOI：
10.1038/aps.2013.133
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发表时间：
2014-01-01
影响因子：
8.2
通讯作者：
Zhao, Jia-jun
中科院分区：
文献类型：
--
作者：
Cai, Hu;Wang, Zhe;Zhao, Jia-jun
目的：目的：研究薯蓣皂苷元（Diosgenin，Dio）对Graves病（Graves' disease，GD）小鼠甲状腺肿形成的影响及其机制。用Dio（20，100 mg.kg（-1）.d（-1），ip）处理小鼠12或24天。采用放射免疫法和电化学发光法检测血清TT 4和TRAb水平。检查甲状腺的大小和形态。用BrdU掺入法测定甲状腺细胞增殖。采用免疫组化和实时荧光定量PCR方法检测GD小鼠甲状腺组织中增殖相关蛋白IGF-1、NF-κ B、cyclin D1和PCNA的表达。Dio处理GD小鼠24 d，剂量依赖性地降低TT 4水平和甲状腺大小，但不影响TRAb的异常水平。此外，Dio处理剂量依赖性地逆转了GD小鼠甲状腺中的形态学变化并减少了甲状腺细胞过度增殖。Dio处理还剂量依赖性地降低GD小鼠甲状腺中IGF-1、NF-κ B、细胞周期蛋白D1和PCNA的mRNA和蛋白水平。结论：Dio通过抑制甲状腺细胞增殖减轻GD小鼠模型中的甲状腺肿。其机制涉及抑制IGF-1、NF-κ B B、cyclin D1和PCNA表达。
Aim: To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms.Methods: Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were treated with Dio (20, 100 mg.kg(-1).d(-1), ip) for 12 or 24 d. The serum levels of TT4 and TRAb were examined using radioimmunoassay and electrochemiluminescence. The size and morphology of thyroid glands were examined. Thyrocyte proliferation was determined using BrdU incorporation assay. The expression of proliferation-associated proteins IGF-1, NF-kappa B, cyclin D1, and PCNA in thyroids was analyzed using immunohistochemistry and real-time PCR.Results: The GD mice showed significantly high serum levels of TRAb and TT4 compared to the normal mice. Treatment of the GD mice with Dio for 24 d dose-dependently reduced the TT4 level and thyroid size, but did not affect the abnormal level of TRAb. Furthermore, Dio treatment dose-dependently reversed the morphological changes and reduced excessive thyrocyte proliferation in thyroids of the GD mice. Dio treatment also dose-dependently reduced the mRNA and protein levels of IGF-1, NF-kappa B, cyclin D1, and PCNA in thyroids of the GD mice.Conclusion: Dio relieves goiter in a mouse model of GD through the inhibition of thyrocyte proliferation. The mechanisms involve the suppression of IGF-1, NF-kappa B, cyclin D1, and PCNA expression.