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朝藿定 C 通过 TGF-β/SMAD 信号通路调节 Treg/Th17 失衡减轻反复自然流产小鼠模型的复发。

Icaritin attenuates recurrent spontaneous abortion in mice by modulating Treg/Th17 imbalance via TGF-β/SMAD signaling pathway.

机构信息

Department of Gynecology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.

College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

Biochim Biophys Acta Mol Cell Res. 2024 Jan;1871(1):119574. doi: 10.1016/j.bbamcr.2023.119574. Epub 2023 Sep 7.

DOI:10.1016/j.bbamcr.2023.119574
PMID:37689142
Abstract

Recurrent spontaneous abortion (RSA) is a challenging global issue. Although the cause is unknown, increasing evidence suggests that immunological factors play a crucial role in RSA development. Icaritin (ICT), a natural compound derived from Epimedium, has demonstrated diverse biological activities, including anti-inflammatory, anti-cancer, and immunomodulatory effects. In this study, we aimed to investigate the potential therapeutic role of ICT in mitigating RSA in a mouse model. Specifically, we sought to determine whether ICT could modulate the Treg/Th17 cell imbalance via the TGF-β/SMAD signaling pathway and contributed to improved pregnancy outcomes. We conducted experiments on a mouse model with RSA and administered ICT orally. We then examined the effects of ICT on various types of immune cells including Treg and Th17 cells, and assessed the pregnancy outcomes. We also investigated the potential signaling pathway ICT exerted its effects. Our findings revealed that treatment with ICT led to an increase in Treg cells and a decrease in Th17 cells, which restored immune homeostasis and contributed to improved pregnancy outcomes. Furthermore, our data demonstrated that ICT's effects were mediated through the activation of TGF-β/SMAD signaling components. In conclusion, our study suggested that ICT ameliorated RSA by modulating Treg/Th17 cell imbalance via the TGF-β/SMAD signaling pathway. GENERAL SIGNIFICANCE: Our results highlighted the potential of ICT as a novel therapeutic agent for RSA, offering new insights into the underlying mechanisms and opening avenues for future research and clinical translation.

摘要

复发性自然流产(RSA)是一个具有挑战性的全球性问题。虽然其病因不明,但越来越多的证据表明免疫因素在 RSA 的发展中起着至关重要的作用。淫羊藿素(ICT)是从淫羊藿中提取的一种天然化合物,具有多种生物学活性,包括抗炎、抗癌和免疫调节作用。在这项研究中,我们旨在研究 ICT 在减轻小鼠 RSA 模型中的潜在治疗作用。具体来说,我们试图确定 ICT 是否可以通过 TGF-β/SMAD 信号通路来调节 Treg/Th17 细胞失衡,并有助于改善妊娠结局。我们在 RSA 小鼠模型中进行了实验,并口服给予 ICT。然后,我们检查了 ICT 对各种免疫细胞(包括 Treg 和 Th17 细胞)的影响,并评估了妊娠结局。我们还研究了 ICT 发挥作用的潜在信号通路。我们的研究结果表明,ICT 治疗导致 Treg 细胞增加,Th17 细胞减少,从而恢复免疫平衡并有助于改善妊娠结局。此外,我们的数据表明,ICT 的作用是通过激活 TGF-β/SMAD 信号通路成分介导的。总之,我们的研究表明,ICT 通过 TGF-β/SMAD 信号通路调节 Treg/Th17 细胞失衡来改善 RSA。一般意义:我们的研究结果强调了 ICT 作为 RSA 新型治疗剂的潜力,为潜在机制提供了新的见解,并为未来的研究和临床转化开辟了途径。

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