Unfractionated heparin inhibits histone-mediated coagulation activation and thrombosis in mice
Unfractionated heparin inhibits histone-mediated coagulation activation and thrombosis in mice
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DOI：
10.1016/j.thromres.2020.06.007
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发表时间：
2020-09-01
影响因子：
7.5
通讯作者：
Li, Xu
中科院分区：
文献类型：
--
作者：
Li, Lu;Yu, Sihan;Li, Xu
引言：组蛋白在脓毒症的病理生理学中起关键作用。不同的研究报告，普通肝素（UFH）可以改善组蛋白介导的器官功能障碍。然而，在此类研究中，UFH通常是预处理或同时注射组蛋白，这显然与临床实践不符。因此，本研究旨在弄清楚是否UFH可以抑制组蛋白诱导的凝血激活和血栓形成时，组蛋白已经引起凝血disorders.Methods：雄性C57/BL 6小鼠，平均体重接近22 g随机分为三组。组蛋白组经尾静脉注射组蛋白50 mg/kg。组蛋白+ UFH组在组蛋白诱导后1 h或6 h经尾静脉注射UFH（400 U/kg）。对照组注射等体积的无菌生理盐水。UFH给药后3 h收获肺。在生存研究中，小鼠接受UFH治疗，（800 U/kg，n = 10）或无菌生理盐水（n = 10），组蛋白结果：1）UFH能提高致死剂量组蛋白小鼠的存活率，2）UFH能减轻组蛋白所致的肺损伤和肺水肿，3）UFH能减轻组蛋白所致的内皮细胞损伤，4）UFH能减轻组蛋白所致的肺水肿，5）UFH能减轻组蛋白所致的肺水肿。4）UFH可改善组蛋白介导的TF、派-1、纤维蛋白原的高表达和TM的低表达。结论：UFH可有效减轻组蛋白诱导的肺损伤、凝血激活和血栓形成。
Introduction: Histones play pivotal roles in the pathophysiology of sepsis. Different studies have reported that unfractionated heparin (UFH) can improve histone-mediated organ dysfunction. However, in such studies, UFH was usually pretreated or injected with histones concurrently, which was obviously inconsistent with clinical practice. Therefore, this study aimed to figure out whether UFH can inhibit histone-induced coagulation activation and thrombosis when histones have caused coagulation disorder already.Methods: Male C57/BL6 mice of average weight similar to 22 g were randomly divided into three groups. The histone group was injected with histones 50 mg/kg through the tail vein. The histone + UFH group was injected with UFH (400 U/kg) through the tail vein 1 h or 6 h after the induction of histones. The control group was injected with equal volume of sterile saline. The lungs were harvested 3 h after UFH administration. In survival studies, mice were treated with UFH (800 U/kg, n = 10) or sterile saline (n = 10) intravenously after histones (75 mg/kg) injection and observed for 7 days.Results: 1) UFH improved survival rate in mice injected with lethal doses of histones; 2) UFH alleviated histoneinduced lung injury and pulmonary edema; 3) UFH improved histone-induced endothelial cell injury; 4) UFH improved histone-mediated high expression of TF, PAI-1, fibrinogen and low expression of TM.Conclusion: UFH can effectively attenuate histone-induced lung injury, coagulation activation and thrombosis.