PMID- 32010252
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 19
IP  - 2
DP  - 2020 Feb
TI  - Both UFH and NAH alleviate shedding of endothelial glycocalyx and coagulopathy in 
      LPS-induced sepsis.
PG  - 913-922
LID - 10.3892/etm.2019.8285 [doi]
AB  - 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-alpha 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.
CI  - Copyright: (c) Huang et al.
FAU - Huang, Xiao
AU  - Huang X
AD  - Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical 
      University Hospital, Binzhou, Shandong 256603, P.R. China.
FAU - Han, Shasha
AU  - Han S
AD  - Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical 
      University Hospital, Binzhou, Shandong 256603, P.R. China.
FAU - Liu, Xiangyong
AU  - Liu X
AD  - Department of Cell Biology, Binzhou Medical University, Yantai, Shandong 264003, 
      P.R. China.
FAU - Wang, Tao
AU  - Wang T
AD  - Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical 
      University Hospital, Binzhou, Shandong 256603, P.R. China.
FAU - Xu, Haixiao
AU  - Xu H
AD  - Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical 
      University Hospital, Binzhou, Shandong 256603, P.R. China.
FAU - Xia, Bingyan
AU  - Xia B
AD  - Department of Clinical Laboratory, Yantai Affiliated Hospital of Binzhou Medical 
      University, Yantai, Shandong 264003, P.R. China.
FAU - Kong, Guiqing
AU  - Kong G
AD  - Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical 
      University Hospital, Binzhou, Shandong 256603, P.R. China.
FAU - Li, Jiankui
AU  - Li J
AD  - Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical 
      University Hospital, Binzhou, Shandong 256603, P.R. China.
FAU - Zhu, Weiwei
AU  - Zhu W
AD  - Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical 
      University Hospital, Binzhou, Shandong 256603, P.R. China.
FAU - Hu, Haoran
AU  - Hu H
AD  - Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical 
      University Hospital, Binzhou, Shandong 256603, P.R. China.
FAU - Hao, Dong
AU  - Hao D
AD  - Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical 
      University Hospital, Binzhou, Shandong 256603, P.R. China.
FAU - Wang, Xiaozhi
AU  - Wang X
AD  - Department of Respiratory Medicine and Intensive Care Unit, Binzhou Medical 
      University Hospital, Binzhou, Shandong 256603, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20191205
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC6966138
OTO - NOTNLM
OT  - N-acetylheparin
OT  - coagulation
OT  - glycocalyx
OT  - sepsis
OT  - unfractionated heparin
EDAT- 2020/02/06 06:00
MHDA- 2020/02/06 06:01
PMCR- 2019/12/05
CRDT- 2020/02/04 06:00
PHST- 2019/04/10 00:00 [received]
PHST- 2019/11/13 00:00 [accepted]
PHST- 2020/02/04 06:00 [entrez]
PHST- 2020/02/06 06:00 [pubmed]
PHST- 2020/02/06 06:01 [medline]
PHST- 2019/12/05 00:00 [pmc-release]
AID - ETM-0-0-8285 [pii]
AID - 10.3892/etm.2019.8285 [doi]
PST - ppublish
SO  - Exp Ther Med. 2020 Feb;19(2):913-922. doi: 10.3892/etm.2019.8285. Epub 2019 Dec 
      5.