Unfractionated heparin attenuates lung vascular leak in a mouse model of sepsis:Role of RhoA/Rho kinase pathway

• Published in: Thrombosis research 2013-07, Vol.132 (1), p.e42-e47
• Main Authors: Han, Jiali, Ding, Renyu, Zhao, Dongmei, Zhang, Zhidan, Ma, Xiaochun
• Format: Article
• Language: English
• Subjects: acute lung injury; Animals; Anticoagulants - pharmacology; Anticoagulants - therapeutic use; Capillary Leak Syndrome - chemically induced; Capillary Leak Syndrome - drug therapy; Capillary Leak Syndrome - enzymology; Capillary Leak Syndrome - pathology; Capillary Permeability - drug effects; Disease Models, Animal; Edema - chemically induced; Edema - drug therapy; Edema - enzymology; Edema - pathology; Enzyme Activation - drug effects; Hematology, Oncology and Palliative Medicine; Heparin - pharmacology; Heparin - therapeutic use; Lipopolysaccharides; Lung - blood supply; Lung - drug effects; Lung - pathology; Male; Mice; Mice, Inbred C57BL; Random Allocation; rho-Associated Kinases - metabolism; RhoA; ROCK; sepsis; Sepsis - chemically induced; Sepsis - drug therapy; Sepsis - enzymology; Sepsis - pathology; Signal Transduction - drug effects; unfractionated heparin; vascular barrier function
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2013.03.010

Abstract Introduction Excessive vascular permeability is a characteristic feature of ALI. We have previously demonstrated that UFH prevents LPS-induced disruption of endothelial barrier function in vitro. It was the objective of this study to determine whether UFH may attenuate endotoxin-induced lung vascular leak in mice and to further explore the possible underlying mechanisms. Methods C57BL/6J mice were randomly divided into the control, LPS and LPS plus UFH groups. Sepsis was induced by intraperitoneal injection of LPS at a dose of 30 mg/kg. Mice in the LPS plus UFH group were intravenously received 8 units UFH (heparin sodium) diluted in 20 μl sterile saline at 0.5 h before the injection of LPS. Results 1) UFH pretreatment attenuated LPS-induced histopathological changes in Lung at 6 h; 2) Pretreatment of mice with UFH ameliorated LPS-induced lung edema and lung vascular leak at 6 h; 3) UFH pretreatment dramatically inhibited RhoA and ROCK activation in the lung tissues of LPS-treated mice (3 and 6 h). 4) UFH pretreatment significantly down-regulated ROCK1 gene expression, but did not affect the increased expression of ROCK2 mRNA in the lung tissues of LPS-treated mice at 3 or 6 h. Conclusion These data suggest that UFH may attenuate endotoxin-induced lung vascular leak by regulating RhoA/Rho kinase pathway.