Levels Of Serum VEGF-C/D And CXCL-12 In Diabetic Nephropathy And Clinic Value

Background:Diabetes mellitus(DM)is a chronic metabolic diseasecharacterized by long-term blood glucose rise,which has seriously affected people's quality of life and health.Among the chronic microvascular complications of diabetes mellitus,diabetic nephropathy(DN)plays an important role,which has become the main risk factor of end-stage renal disease in China and the main source of renal replacement therapy.The process of the occurrence and development of diabetic nephropathy has not been fully defined.At present,it has been found that its pathogenesis mainly includes inflammatory response,oxidative stress,renal hemodynamic changes,metabolic abnormalities and genetic factors.At present,the clinical markers for the diagnosis of diabetic nephropathy are mainly glomerular filtration rate,urinary microalbumin excretion rate,creatinine,urea nitrogen,serum cystatin C,etc.Although these indicators can effectively evaluate the function of the kidney,they only indicate the late changes of renal function,and can not reflect the early structural changes of the kidney.Vascular endothelial growth factors(VEGF)belong to the family of platelet-derived growth factors,which play an important role in regulating angiogenesis and lymphangiogenesis.Many studies have found that in the development of diabetic nephropathy,with the increase of lymphangiogenesis,and can reduce the degree of renal inflammation and fibrosis.Chemokine-12(cxcl-12),also known as stromal cell derived factor-1(SDF-1),is a small molecule cytokine,belonging to the chemokine protein family.Some studies have shown that cxcl-12 and its receptor CXCR-4 have strong chemotaxis on lymphocytes,and the cxcl-12 /CXCR-4 signal axis is independent of VEGF-C / D signal axis to promote lymph node metastasis Blocking the vegf-vegfr-3 pathway had no significant effect on the activity of cxcl-12-induced lymphangiogenesis.This shows that lymphangiogenesis is closely related to the development of diabetic nephropathy.Therefore,we propose tospeculate whether lymphangiogenesis factor can be used as a marker for early diagnosis of diabetic nephropathy,and whether it has any effect on the treatment of diabetic nephropathy by inhibiting or promoting lymphangiogenesis.In this study,we observed the expression trend of serum VEGF-C,VEGF-D and cxcl-12 levels in patients with different stages of diabetic nephropathy and their correlation with clinical indicators,so as to provide new ideas for the early diagnosis of diabetic nephropathy.Objects and methods:By prospective observation method,90 patients with type 2 diabetes were divided into three groups according to the level of urinary microalbumin: group A,group B,group C,group A and Group D.The serum VEGF-C,VEGF-D and cxcl-12 were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to analyze the correlation among the observed indexes;ROC was drawn to analyze the value of VEGF-C,VEGF-D and cxcl-12 levels in serum for early diagnosis and severity evaluation of type 2 diabetic nephropathy.Result:1.Compared with the control group,the levels of VEGF-C,VEGF-D and cxcl-12 in the serum of type 2 diabetic nephropathy group were significantly higher,and group C > group B > group A,P < 0.05;2.The correlation analysis showed that the levels of VEGF-C,VEGF-D and cxcl-12 in serum were positively correlated with serum creatinine and urinary microalbumin,and negatively correlated with estimated glomerular filtration rate;3.ROC curve analysis showed that the area under ROC curve(AUG)of normal albuminuria group,microalbuminuria group and massive albuminuria group was0.668(95% CI: 0.531-0.805),0.799(95% CI: 0.678-0.920),0.850(95% CI:0.756-0.944),respectively.When the cutoff value was 152.40,196.05,214.60pg/ml,the sensitivity was 93.3%,96.7%,100.0%,respectively,The specificity was 40.0%,50.0% and 56.7% respectively.The area under ROC curve of normal albuminuria group,microalbuminuria group and large albuminuria group was larger than that of vegf-c.Conclusion:1.The increased expression of VEGF-C,VEGF-D and cxcl-12 in diabetic nephropathy suggests that lymphangiogenesis may be involved in the progression of diabetic nephropathy,which is related to the renal damage of diabetic nephropathy.2.The levels of VEGF-C,VEGF-D and cxcl-12 in serum were positively correlated with serum creatinine and urinary microalbumin,and negatively correlated with estimated glomerular filtration rate.3.The expression of VEGF-C,VEGF-D and cxcl-12 in serum has a certain value in the early diagnosis of diabetic kidney,at least can be used to predict the progress of the disease.