Both UFH and NAH alleviate shedding of endothelial glycocalyx and coagulopathy in LPS‑induced sepsis

Huang,Xiao; Han,Shasha; Liu,Xiangyong; Wang,Tao; Xu,Haixiao; Xia,Bingyan; Kong,Guiqing; Li,Jiankui; Zhu,Weiwei; Hu,Haoran; Hao,Dong; Wang,Xiaozhi

doi:10.3892/etm.2019.8285

Both UFH and NAH alleviate shedding of endothelial glycocalyx and coagulopathy in LPS‑induced sepsis

Authors:
- Xiao Huang
- Shasha Han
- Xiangyong Liu
- Tao Wang
- Haixiao Xu
- Bingyan Xia
- Guiqing Kong
- Jiankui Li
- Weiwei Zhu
- Haoran Hu
- Dong Hao
- Xiaozhi Wang
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Affiliations: Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China, Department of Cell Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Clinical Laboratory, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Published online on: December 5, 2019 https://doi.org/10.3892/etm.2019.8285
Pages: 913-922
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sepsis commonly progresses to disseminated intravascular coagulation and induces the activation of heparanase (HPA) and the shedding of endothelial glycocalyx constituents, including syndecan‑1 (SDC‑1) and heparan sulphate (HS). However, the degradation of glycocalyx and its association with coagulation disorders remains undetermined. The present study aimed to evaluate the effect of unfractionated heparin (UFH) and N‑acetylheparin (NAH), which is a non‑anticoagulant heparin derivative, on endothelial glycocalyx and coagulation function in a lipopolysaccharide (LPS)‑induced sepsis rat model, and to compare the differences observed in coagulation function between UFH and NAH. Experimental rats were randomly assigned to four groups: Control; LPS; UFH + LPS; and NAH + LPS. Rats were administered UFH or NAH and subsequently, ~1 min later, administered LPS (10 mg/kg; intravenous). The blood and lung tissues of rats were collected 0.5, 2 and 6 h after LPS injection, and were used for subsequent analysis. The results demonstrated that HPA activity and SDC‑1 and HS levels increased, and this increase was associated with inflammatory cytokines and coagulation/fibrinolysis markers in the sepsis rat model. Histopathological examination was performed, and the lung injury score and lung wet/dry ratio indicated that UFH and NAH also significantly improved lung tissue injury. The results of the ELISA analysis demonstrated that UFH and NAH treatment: i) significantly decreased the levels of inflammatory cytokines including tumor necrosis factor‑α and interleukin‑6; ii) inhibited HPA activity and protected the integrity of the glycocalyx, which was identified by decreased HS and SDC‑1 levels; and iii) decreased the levels of prothrombin fragment 1+2, thrombin‑antithrombin complex, and plasminogen activator inhibitor‑1 and increased the levels of fibrinogen and antithrombin‑III. Preconditioning with UFH decreased the plasma activated partial thromboplastin time. These results indicated that UFH and NAH may alleviate sepsis‑induced coagulopathy, and this effect may have been due to an inhibition of HPA activity and decrease in the shedding of the endothelial glycocalyx.

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