Impact of heparanase on glomerular endothelium glycocalyx during sepsis
10.3760/cma.j.issn.1001-7097.2014.07.008
- VernacularTitle:乙酰肝素酶对脓毒症肾小球内皮细胞糖萼的影响
- Author:
Zengbo LIU
;
Changlin MEI
;
Huimin HU
;
Xueqi WANG
;
Lili FU
- Publication Type:Journal Article
- Keywords:
Sepsis;
Heparin lyase;
Glomerular endothelium;
Glycocalyx;
Heparanase;
Heparin
- From:
Chinese Journal of Nephrology
2014;30(7):524-529
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the impact of heparanase on glomerular endothelium glycocalyx during sepsis and to investigate the prevention of glycocalyx injury.Methods C57/BL6 mice were injected with lipopolysaccharide (LPS) or tumor necrosis factor-α(TNF-o) and sacrificed one hour later.Glomerular endothelium glycocalyx traced with lanthanum was observed by transmission electron microscope(TEM).Western blotting was used to observe heparanse protein expression of renal cortex tissue.Human renal glomerular endothelial cells (HRGECs) were stimulated with TNF-α and active heparanase protien expression was detected by Western blotting.Mice were administrated with heparin sodium or heparinase Ⅲ and renal endothelium glycocalyx was observed by TEM.Urine during twenty-four hours was collected to measure urinary albumin and creatinine.The ratio of albumin to creatinine was calculated and compared among groups.Results The glomerular endothelium glycocalyx of LPS group and TNF-α group was degradated and the one of podocyte was integrated.Renal cortex tissue heparanase protein expression was significantly increased since one hour after LPS injection (P < 0.01).The protein expression of activited heparanase of HRGECs which were stimulated with TNF-α was increased (P < 0.05).Administration of heparin sodium which could inhibit the activity of heparanase could prevent the glycocalyx form degradation.The ratio of urine albumin to creatinine of heparin sodium group was decreased compared with LPS group (P < 0.05) and the ratio of heparinase Ⅲ group was higher than control group(P < 0.01) as a result of degradation of glomerular endothelium glycocalyx.Conclusions During the early stage of sepsis,TNF-α can induce glomerular endothelium heparanase to increase and active,and consequently the glycocalyx is degradated which leads to albuminuria.Inhibition of heparanase can protect glomerular endothelium glycocalyx and prevent albuminuria.