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寿胎丸上调母胎界面 TNFAIP3 的表达,改善 T 细胞免疫耐受。

Shoutai Wan treatment upregulates the expression of TNFAIP3 and improves T cell immune tolerance at maternal-fetal interface.

机构信息

Department of traditional Chinese Medicine, Pizhou people's Hospital affiliated to Xuzhou Medical University, Jiangsu 221000, China.

Department of Obstetrics and Gynecology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200000, China.

出版信息

J Reprod Immunol. 2024 Sep;165:104301. doi: 10.1016/j.jri.2024.104301. Epub 2024 Jul 14.

Abstract

Shoutai Wan (STW) is a traditional Chinese medicine formula used to treat various conditions. The objective of this study was to evaluate the impact of STW on the abortion rate in the URSA mouse model and elucidate its underlying molecular mechanisms. Female CBA/J mice were mated with male DBA/2 mice to establish the URSA model. Network pharmacological analysis was employed to investigate the potential molecular mechanisms of STW. Hematoxylin-eosin staining, immunofluorescence, and ELISA were performed to examine placental microenvironmental changes, protein expression related to TNFAIP3 and the NF-κB signaling pathway. Treatment with STW reduced the abortion rate in URSA model mice and improved trophoblast development. TNFAIP3 was identified as a potential target of STW for treating URSA, as STW enhanced TNFAIP3 protein expression while decreasing IL-6 and TNF-α secretion in the placenta. Moreover, STW upregulated TNFAIP3 protein expression and Foxp3 mRNA levels, increased the production of anti-inflammatory cytokines such as IL-10 and TGF-β1, and decreased p-NF-κB expression in CD4+ cells at the placenta. The findings of this study indicate that STW treatment reduces the abortion rate in the URSA mouse model. These effects are likely mediated by increased TNFAIP3 expression and decreased NF-κB signaling pathway activity at the maternal-fetal interface. These molecular changes may contribute to the regulation of T cell immunity and immune tolerance during pregnancy.

摘要

寿胎丸(STW)是一种用于治疗各种疾病的中药方剂。本研究旨在评估 STW 对 URSA 小鼠模型流产率的影响,并阐明其潜在的分子机制。将 CBA/J 雌性小鼠与 DBA/2 雄性小鼠交配,建立 URSA 模型。采用网络药理学分析方法研究 STW 的潜在分子机制。进行苏木精-伊红染色、免疫荧光和 ELISA 检测,以检查胎盘微环境变化、与 TNFAIP3 和 NF-κB 信号通路相关的蛋白表达。STW 降低了 URSA 模型小鼠的流产率,并改善了滋养层发育。TNFAIP3 被鉴定为 STW 治疗 URSA 的潜在靶标,因为 STW 增强了胎盘 TNFAIP3 蛋白表达,同时减少了 IL-6 和 TNF-α 的分泌。此外,STW 增加了胎盘 CD4+细胞中 TNFAIP3 蛋白表达和 Foxp3 mRNA 水平,增加了抗炎细胞因子如 IL-10 和 TGF-β1 的产生,并降低了 p-NF-κB 的表达。本研究结果表明,STW 治疗可降低 URSA 小鼠模型的流产率。这些作用可能是通过增加 TNFAIP3 表达和降低母胎界面 NF-κB 信号通路活性介导的。这些分子变化可能有助于调节妊娠期间 T 细胞免疫和免疫耐受。

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