| ObjectiveDiabetic nephropathies (DN) is one of the most important complications of diabetes mellitus ( DM ). The etiology and mechanism of DN has not been illustrated completely. Previous researches proved that various of cytokines were involved in the pathogenesis of DN through autocrine, paracrine and endocrine.Vascular endothelial growth factor( VEGF) , also called vascular permeability factor (VPF) , is a homodimeric glycoprotein consisting of two identical poly-peptide chains, which is combined by disulfate bond. The major biological functions of VEGF are potent vascular permeablity and specific endothelial mitogen -promoting angiogenesis. With these actions, it is viewed that VEGF play a key role in various macrovascular and microvascular disease through intervening functional disarrangement of endothelial cells.Disfunction of endothelial cells contributes to the pathogenesis of microvascular complications of DM. Since DN is one of the important DM microvascular complications, disfunction of endothelial cell must play a role in its pathogenesis.In this study, we detected the change of plasma vascular endothelial growth factor (VEGF) level in patients with diabetic nephropathies ( DN ) in different stages so as to explicit the correlation between vascular endothelial growth factor and diabetic nephropathies. Moreover, an intervention study of angiotensin II receptor blockers ( ARBs )--losartan was processed. By studying the influenceof losartan on plasma VEGF level, we tried to know the regulation action of AT II on VEGF so as to discuss the mechanism of DN more.Materials and Methods89 cases of type 2 diabetes mellitus patients were divided into three groups according to urine albumium excretion rate ( UAER) : normoalbuminuria group ( NA, 30 ); microalbuminuria group ( MA, 29 ) ; macroalbuminuria group (ODN, 30). 20 cases are healthy subjects ( controls). Plasma VEGF,FBG, HbA1c ,BUN, Cr were detected in all cases. MA group and ODN group were respectively devided into two groups: group treated with losartan ( MA I group and ODN I group) and group treated with routine method ( MA I group and ODN I group). The change of UAER and VEGF were studied after intervention treatment. VEGF is detected by ELISA.Comparisions were made by analysis of variance ( ANOVA) within groups and by compared t - test between groups using a SPSS for Windows computer ap-plicaton. Simple regression analysis was also used.ResultsCompared with control group, plasma level of VEGF significantly increased in NA group, MA group and ODN group. Plasma VEGF gradually increased in NC,NA,MA and ODN group( P <0. 01). Regression analysis shows that plasma VEGF was in positive correlation with UAER,Cr and HbA1c. In MA I group and ODN I group, plasma VEGF and UAER had significantly decreased after treatment with lorsartan ( P < 0. 05 or P < 0. 01).DiscussionThis study indicated that plasma level of VEGF had already significantly increased in the early stage of DN patients. Accompanied with the development of DN, plasma level of VEGF in patients jgradually increases, at the same time, plasma level of VEGF is positively correlated with Cr and UAER. Above proved that VEGF is involved in the pathogenesis of DN.The change of VEGF plasma level is positively correlated with UAER, supporting the hypothesis that VEGF promotes the generation of albumia urine. VEGF is the most potent permeability factor we know at present, meanwhile, VEGF continuously express on podocytes in kidney, with combining site mainly limited on glomerulus endothelial cells. This dissetion localization supports that VEGF may have regulation action on glomerulus permeablity. The production of VEGF increases in DM patients, then the upregulation of VEGF makes effect to increase glomerulus permeablity. Previous researches also suggest the effect of VEGF on the generation of albumia urine in DN patients. This study demonstrated that VEGF plasma level was positively correlated with albumia urine level, consistent with previous research, also supporting...
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