A&R:抗磷脂抗体通过Toll样受体4、活性氧和p38 MAPK信号传导增加子宫内膜基质细胞蜕膜、衰老和炎症

2022-06-18 MedSci原创 MedSci原创

抗磷脂抗体增加了人类子宫内膜基质细胞蜕膜、衰老和炎症,为抗磷脂自身抗体阳性女性妊娠并发症的发病机制提供了新的线索,并强调了肝素在预防这一高危人群流产方面的益处。

目的:流产影响七分之一的妊娠,抗磷脂自身抗体(aPL)是复发性流产的最大风险因素之一。虽然aPL以子宫内膜基质为目标,但对其影响知之甚少。子宫内膜基质细胞(EnSC) 在每个月经周期都会经历蜕膜化,从而使子宫能够接受植入的胚胎。因此,适当的蜕膜化和EnSC功能是成功妊娠的关键。本研究旨在探索aPLEnSC蜕膜、衰老和炎症的影响。

方法蜕膜条件下的EnSC单独暴露于aPL或对照IgG,或在Toll样受体4 (TLR-4)拮抗剂、p38 MAPK(丝裂原活化蛋白激酶)抑制剂、活性氧(ROS)抑制剂、低分子量肝素(LMWH)或乙酰水杨酸存在的情况下。通过酶联免疫吸附测定蜕膜标志物和炎性白细胞介素8的分泌,并评估衰老相关的β-半乳糖苷酶活性。在蜕膜化小鼠模型中,给予aPL或对照IgG,并通过实时定量聚合酶链反应对蜕膜化和炎症标志物的子宫表达水平进行量化。

结果:抗磷脂抗体增加了人类EnSC蜕膜、衰老和炎症。这些表型在小鼠模型中得到了复制。蜕膜化和炎症反应部分由TLR-4p38 MAPK介导,而蜕膜化和衰老反应是ROS依赖性的。LMWH通常用于治疗有产科并发症风险的aPL阳性妇女,它降低了aPL增加EnSC蜕膜和炎症的能力。

结论这些发现为抗磷脂自身抗体阳性女性妊娠并发症的发病机制提供了新的线索,并强调了肝素在预防这一高危人群流产方面的益处。

出处:Tong, M., Kayani, T., Jones, D.M., Salmon, J.E., Whirledge, S., Chamley, L.W. and Abrahams, V.M. (2022), Antiphospholipid Antibodies Increase Endometrial Stromal Cell Decidualization, Senescence, and Inflammation via Toll-like Receptor 4, Reactive Oxygen Species, and p38 MAPK Signaling. Arthritis Rheumatol, 74: 1001-1012. https://doi.org/10.1002/art.42068

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    2023-04-21 lidong51
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    2022-06-18 徐岩

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