To Discuss The Mechanism Of Vascular Endothelial Cell Damage By Urate

OBJECTIVE:To observe the role of different concentration of urate in the expression of vascular endothelial cell injury associated factors;To identify the injury of Hyperuricemia on endothelial cells is through direct effects or through the role of monocyte releasing of inflammatory factors in the indirect effects.METHODS:All experiments were performed with human vascular endothelial cells cultured and endothelial cells and monocytes co-cultured in vitro.Control group is non-urate.According to the concentration of urate in culture medium,stimulations were divided in to five groups:L2(the concentration of urate is 395μmol/L ),L1 (789μmol/L),M(1184μmol/L),H1(1579μmol/L),H2(1974μmol/L).The six groups stimulated vascular endothelial cells for 48 hours.The levels of IL-1,TNF-α,ICAM-1 in the supernatants of cell cultures were measured by enzyme linked immunosorbent assay(ELISA).Meanwhile,the expression of hUAT(human urate transporer) mRNA was tested by using RT-PCR.RESULTS:①IL-1,TNF-α:endothelial cells groups:IL-1 and TNF-αexpressions increased in M(1184μmol/L),H1(1579μmol/L),H2(1974μmol/L) groups compared with the control group(P＜0.05),and the expressions in co-cultured groups were significantly higher than that of endothelial cells groups(P＜0.05);②ICAM-1: endothelial cells groups:the expression of ICAM-1 was increased in H2 (1974μmol/L)groups compared with the control group(P＜0.05 ).co-cultured groups: the expression of ICAM-1 was increased in H1(1579μmol/L),H2(1974μmol/L) groups compared with the control group(P＜0.05);③PAI-1:endothelial cells groups: PAI-1 expression increased in H1(1579μmol/L),H2(1974μmol/L) groups compared with the control group(P＜0.05),and in co-cultured groups,high expression of PAI-1 could be tested in M(1184μmol/L ),H1(1579μmol/L),H2(1974μmol/L) groups compared with the control group(P＜0.05);④the expression of hUAT mRNA decreased in H1,H2(1974μmol/L) concentration group in endothelial cells groups and co-cultured groups.CONCLUSIONS:Urate can cause endothelial cells to release inflammatory cytokines and induce inflammatory response,mononuclear cells also played an important role in the process of endothelial cell injury,and high concentration of urate can decrease the expression of hUAT mRNA.