Embelin ameliorated sepsis-induced disseminated intravascular coagulation intensities by simultaneously suppressing inflammation and thrombosis
Embelin ameliorated sepsis-induced disseminated intravascular coagulation intensities by simultaneously suppressing inflammation and thrombosis
复制标题
Embelin 通过同时抑制炎症和血栓形成来改善脓毒症引起的弥散性血管内凝血强度。
DOI：
10.1016/j.biopha.2020.110528
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发表时间：
2020-10-01
影响因子：
7.5
通讯作者：
Xu, Peng
中科院分区：
文献类型：
--
作者：
Wang, Dong;Yang, Yongshuai;Xu, Peng
弥散性血管内凝血（DIC）是全身微血管形成系统性血栓的一种急性综合征，可由严重感染（如败血症）引起。临床上使用抗凝剂来减轻DIC的强度。然而，抗凝剂只能减少血栓的形成，而对炎症的影响可以忽略不计。我们之前报道过天然产物——栓塞素作为纤溶酶原激活物抑制剂-1 （PAI-1）的抑制剂，表明其具有有效的抗血栓特性。在这项研究中，我们使用三种血栓小鼠模型来证实栓塞的抗血栓特性。通过结合抗炎和抗血栓特性，我们提出了栓塞作为脓毒症诱导的DIC的有效治疗剂，包括炎症和血栓形成。在脂多糖诱导的脓毒症小鼠模型中，栓塞不仅能显著改善炎症水平，还能有效减少肺出血和肺微血栓的形成。相比之下，低分子肝素，一种抗凝剂，只能适度改善肺出血和血栓性阻塞，但对炎症条件的影响不可测量。此外，栓塞可减轻脓毒症小鼠全血细胞凝血功能失调，但不影响正常小鼠全血细胞凝血功能。我们目前的研究证明了栓塞的抗血栓特性以及治疗或预防炎症和血栓合并综合征的效力，例如败血症引起的DIC。
Disseminated intravascular coagulation (DIC), an acute syndrome of systemic thrombus formation in microvasculatures throughout the body, can be induced by severe infections, e.g. sepsis. Anticoagulants are clinically used to alleviate the intensities of DIC. However, anticoagulants only reduce the thrombus formation but have negligible effects on the inflammatory conditions. We previously reported embelin, a natural product, as an inhibitor of plasminogen activator inhibitor-1 (PAI-1), suggesting the potent antithrombotic property. In this study, we used three thrombotic mice models to confirm the antithrombotic property of embelin. By combining the anti-inflammatory and the antithrombotic properties, we proposed embelin as a potent therapeutic agent for sepsis-induced DIC, which involves both inflammation and thrombosis. In a lipopolysaccharides-induced septic mice model, embelin not only significantly ameliorated the inflammation levels, but also effectively reduced the pulmonary hemorrhages and the micro-thrombi formations in lung. In contrast, low-molecular-weight-heparin, an anticoagulant, only moderately ameliorated the pulmonary hemorrhages and thrombotic obstructions, but had non-measurable effect on the inflammatory conditions. In addition, embelin alleviated the dysregulation of the global coagulation in septic mice, but did not affect the global coagulation in normal mice. Our current study demonstrates the antithrombotic property of embelin and the potency of the treatment or prevention of syndromes combining inflammation and thrombosis, e.g. sepsis-induced DIC.