Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Sichuan Renal Disease Clinical Research Center, University of Electronic Science and Technology of China, Chengdu, China.
Reprod Sci. 2023 Sep;30(9):2794-2804. doi: 10.1007/s43032-023-01185-0. Epub 2023 Mar 8.
Recurrent spontaneous abortion (RSA) is the most common pregnancy-related complication, affecting 1-5% of pregnancies. Currently, immune imbalance at the maternal-fetal interface is one of the main causes of recurrent abortion. Icariin (ICA) can exert immunomodulatory effects in a variety of autoimmune diseases. Nevertheless, it has not been reported for use in recurrent abortion. In this study, to clarify the effects and mechanisms of ICA for recurrent abortion, female mice CBA/J were randomly divided into Normal group, RSA group and RSA + ICA group. From 0.5 days of pregnancy to 12.5 days, the RSA + ICA group was subjected to orally ICA (50 mg/Kg) daily, and the Normal group and the RSA group were given with an equal volume of distilled water. The results showed the amount of reabsorbed embryo in the RSA group was significantly higher than that in the normal-pregnancy group. However, ICA treatment showed a rescue effect on spontaneous abortion in RSA mice. ICA was able to increase the ratio of the labyrinth to total placental area in abortion-prone model. Further investigation showed that ICA treatment can expand the regulatory T cell (Treg) population in mice prone to abortion, significantly decrease the populations of Th1 cells, and reduce the expression of pro-inflammatory factors. Additionally, ICA treatment was able to decrease the expression of mechanical target of rapamycin (mTOR) in the placenta. ICA may increase Treg cell expansion and reducing pro-inflammatory factors expression via the mTOR pathway, then reducing placental inflammation and improving pregnancy outcomes in abortion-prone mice.
复发性自然流产(RSA)是最常见的妊娠相关并发症,影响 1-5%的妊娠。目前,母体-胎儿界面的免疫失衡是复发性流产的主要原因之一。淫羊藿苷(ICA)在多种自身免疫性疾病中具有免疫调节作用。然而,它尚未被报道用于复发性流产。在这项研究中,为了阐明 ICA 对复发性流产的作用及其机制,将雌性 CBA/J 小鼠随机分为正常组、RSA 组和 RSA+ICA 组。从妊娠 0.5 天到 12.5 天,RSA+ICA 组每日口服 ICA(50mg/Kg),正常组和 RSA 组给予等体积蒸馏水。结果表明,RSA 组胚胎吸收量明显高于正常妊娠组。然而,ICA 治疗对 RSA 小鼠的自然流产具有挽救作用。ICA 能够增加流产易感模型中绒毛膜的比例。进一步的研究表明,ICA 治疗能够增加易流产小鼠的调节性 T 细胞(Treg)群体,显著减少 Th1 细胞的数量,并降低促炎因子的表达。此外,ICA 治疗能够降低胎盘中机械靶蛋白激酶(mTOR)的表达。ICA 可能通过 mTOR 通路增加 Treg 细胞的扩增和减少促炎因子的表达,从而减少胎盘炎症并改善易流产小鼠的妊娠结局。