Department of Critical Care Medicine, the First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang, 110001, Liaoning Province, People's Republic of China.
Inflammation. 2022 Apr;45(2):712-724. doi: 10.1007/s10753-021-01578-w. Epub 2021 Oct 16.
Endothelial glycocalyx degradation is thought to facilitate the development of sepsis. Histone is a significant mediator in sepsis. Unfractionated heparin (UFH) possessed beneficial effects on sepsis. Thereby, this study aims to figure out whether histone can disrupt glycocalyx and to investigate the protective effect and mechanism of UFH. Male mice (C57BL/6, 8-10 weeks old, weighing 20-25 g) were randomly divided into five groups including control group, histone group, histone + UFH group, histone + heparinase (HPA) inhibitor group, and histone + UFH + HPA inhibitor group. The mice were treated with histone (50 mg/kg) via tail vein immediately after HPA (20 mg/kg) injection. UFH (400 U/kg) was injected 1h after histone administration. The other groups were injected with equal volume of sterile saline accordingly. UFH alleviated histone-induced lung injury and pulmonary edema. UFH inhibited histone-induced lung coagulation activation and inflammatory response. UFH treatment markedly inhibited pulmonary glycocalyx degradation by reducing the histone-induced decrease in the levels of lung syndecan-1 mRNA and protein. UFH downregulated histone-induced expression of HPA mRNA and protein, and thus alleviated glycocalyx degradation. UFH protects against histone-induced pulmonary glycocalyx injury partly by heparinase pathway.
内皮糖萼降解被认为有助于脓毒症的发展。组蛋白是脓毒症的重要介质。未分级肝素（UFH）对脓毒症具有有益的作用。因此，本研究旨在探讨组蛋白是否可以破坏糖萼，并研究 UFH 的保护作用和机制。雄性小鼠（C57BL/6，8-10 周龄，体重 20-25g）随机分为五组，包括对照组、组蛋白组、组蛋白+UFH 组、组蛋白+HPA 抑制剂组和组蛋白+UFH+HPA 抑制剂组。在 HPA（20mg/kg）注射后，立即通过尾静脉给予小鼠组蛋白（50mg/kg）。UFH（400U/kg）在组蛋白给药 1 小时后注射。其他组相应地注射等体积的无菌生理盐水。UFH 减轻了组蛋白引起的肺损伤和肺水肿。UFH 抑制了组蛋白引起的肺凝血激活和炎症反应。UFH 治疗通过降低组蛋白诱导的肺 syndecan-1 mRNA 和蛋白水平的降低，显著抑制了组蛋白诱导的肺糖萼降解。UFH 下调了组蛋白诱导的 HPA mRNA 和蛋白的表达，从而减轻了糖萼的降解。UFH 通过肝素酶途径部分保护组蛋白诱导的肺糖萼损伤。
