熊去氧胆酸通过TREM2抑制血小板活化和血栓形成：来自小鼠模型和人体研究的证据
Ursodeoxycholic acid inhibits platelet activation and thrombosis via TREM2: Evidence from mouse models and human studies.
摘要(中文译文)
当前抗血小板治疗能有效预防血栓形成，但与出血风险增加相关，凸显了对更安全替代方案的需求。熊去氧胆酸（UDCA）是一种胆汁酸衍生物，具有已确立的临床安全性特征，但其对血小板功能和血栓形成的影响尚不明确。本研究在体外和离体条件下评估了UDCA对人及小鼠血小板活化的影响。在肠系膜小动脉损伤和肺栓塞小鼠模型中评价了抗血栓疗效和出血风险。在健康志愿者口服给药后检测血小板活性，并在急性冠脉综合征患者中探讨了临床相关性。采用分子对接和表面等离子体共振分析配体-受体相互作用，并利用遗传学和生物化学方法研究机制通路。UDCA抑制了人和小鼠的血小板活化，并减少了体内血栓形成，其疗效与氯吡格雷相当，但出血显著减少。口服给药抑制了健康志愿者的血小板活化，接受UDCA治疗的急性冠脉综合征患者血清肌钙蛋白水平较低。UDCA直接结合髓系细胞触发受体2（TREM2），其抗血小板效应在TREM2缺陷血小板中减弱。机制上，UDCA增强了含Src同源2结构域的肌醇磷酸酶1（SHIP1）并抑制了Akt磷酸化。这些发现表明UDCA是一种具有抗血小板和抗血栓活性且出血特征良好的TREM2激动剂，支持其作为血栓性疾病更安全治疗策略的潜力。
Abstract
Current antiplatelet therapies effectively prevent thrombosis but are associated with an increased risk of bleeding, highlighting the need for safer alternatives. Ursodeoxycholic acid (UDCA) is a bile acid derivative with an established clinical safety profile, but its effects on platelet function and thrombosis remain poorly defined. The effects of UDCA on platelet activation were assessed in human and mouse platelets in vitro and ex vivo. Antithrombotic efficacy and bleeding risk were evaluated in murine models of mesenteric arteriole injury and pulmonary embolism. Platelet activity was examined in healthy volunteers following oral administration, and clinical associations were explored in patients with acute coronary syndrome. Ligand-receptor interactions were analysed using molecular docking and surface plasmon resonance, and mechanistic pathways were investigated using genetic and biochemical approaches. UDCA inhibited platelet activation in both human and mouse platelets and reduced thrombus formation in vivo, with efficacy comparable to clopidogrel but significantly less bleeding. Oral administration suppressed platelet activation in healthy volunteers, and patients with acute coronary syndrome receiving UDCA exhibited lower serum troponin levels. UDCA directly bound to triggering receptor expressed on myeloid cells 2 (TREM2), and its antiplatelet effects were attenuated in TREM2-deficient platelets. Mechanistically, UDCA enhanced Src homology 2 domain-containing inositol phosphatase 1 (SHIP1) and suppressed Akt phosphorylation. These findings identify UDCA as a TREM2 agonist with antiplatelet and antithrombotic activity and a favourable bleeding profile, supporting its potential as a safer therapeutic strategy for thrombotic diseases.
如何引用
AMA
Xiaowen Wu, Yulong Zhang, Qingyuan Yang, Liwen Xue, Yifan Guo, Li Li, et al. Ursodeoxycholic acid inhibits platelet activation and thrombosis via TREM2: Evidence from mouse models and human studies.. British journal of pharmacology. 2026; doi:10.1111/bph.70567.
APA
Xiaowen Wu, Yulong Zhang, Qingyuan Yang, Liwen Xue, Yifan Guo, Li Li, et al (2026). Ursodeoxycholic acid inhibits platelet activation and thrombosis via TREM2: Evidence from mouse models and human studies.. British journal of pharmacology. https://doi.org/10.1111/bph.70567
GB/T 7714
Xiaowen Wu, Yulong Zhang, Qingyuan Yang, Liwen Xue, Yifan Guo, Li Li, et al. Ursodeoxycholic acid inhibits platelet activation and thrombosis via TREM2: Evidence from mouse models and human studies.[J]. British journal of pharmacology, 2026 doi:10.1111/bph.70567.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出