Ulinastatin Through Maintain The Integrity Of Glycocalyx To Protective The LPS Induced ARDS Of Mice And Its Mechanism

Background:Located between the endothelium and the blood stream,the endothelial glycocalyx is an important determinant of vascular permeability.Heparanase(HPA)plays a pivotal role in structural remodeling of the glycocalyx.The impact of ulinastatin(UTI)on the pulmonary endothelial glycocalyx of acute respiratory distress syndrome(ARDS)remains unclear.We performed a study to evaluate the effect of UTI on the pulmonary endothelial glycocalyx integrity and inhibit heparanase(HPA)in lipopolysaccharide(LPS)-induced injury.Methods:Serum and lung tissue were collected from 30 C57BL/6 male mice after intraperitoneal injection(i.p.)LPS(10mg/Kg)30 min,inflammatory cytokines(e.g.,TNF-a,IL-6)were tested by serum ELISA.Glycocalyx integrity was observed by transmission electron microscope(TEM)and investigated by analysis of glycocalyx degradation products(e.g.,heparan sulfate)by serum ELISA.HPA activity was tested by serum ELISA.Lung histology was evaluated by hematoxylin and eosin(HE)staining and Wet/dry lung weight ratio.Western blot assay showed that UTI inhibited the expression of HPA in lung tissue and Human umbilical vein endothelial cells.we examined heparanase localization in lysosomes,utilizing immunofluorescent staining.Results:In mice,inflammatory cytokines(e.g.,TNF-a,IL-6),glycocalyx degradation products(e.g.,heparan sulfate),HPA activity and processing were inhibited by UTI both in vivo and in vitro.UTI could memorably protect glycocalyx ultrastructure observed through TEM.Conclusions:UTI effects pulmonary endothelial glycocalyx shedding by inhibits heparanase during LPS-induced injury.