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Unfractionated Heparin Attenuated Histone-Induced Pulmonary Syndecan-1 Degradation in Mice: a Preliminary Study on the Roles of Heparinase Pathway

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Abstract—

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.

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Acknowledgements

We acknowledge all staff who helped perform this study.

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This study was supported by the National Natural Science Foundation of China (Grant No. 81671936).

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  1. 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

    Sifeng Fu, Sihan Yu, Yilin Zhao, Xiaochun Ma & Xu Li

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Conceptualization: Sifeng Fu; methodology: Sihan Yu; formal analysis and investigation: Yilin Zhao; writing — original draft preparation: Sifeng Fu; writing — review and editing: Xu Li; funding acquisition: Xu Li; resources: Xiaochun Ma; Supervision: Xiaochun Ma.

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Correspondence to Xu Li.

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Fu, S., Yu, S., Zhao, Y. et al. Unfractionated Heparin Attenuated Histone-Induced Pulmonary Syndecan-1 Degradation in Mice: a Preliminary Study on the Roles of Heparinase Pathway. Inflammation 45, 712–724 (2022). https://doi.org/10.1007/s10753-021-01578-w

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