The Express Of Serum Pigment Epithelium-derived Factor In Type2Diabetic Patients With Daibetic Nephropathy And Effect Of Valsartan Combined Sodium Ferulate

ObjectivesDiabetic nephropathy is one of the most important microvascular complications andhas become the leading cause of end-stage renal disease worldwide. Several studies haveindicated that abnormal angiogenesis occurs in diabetic nephropathy. Pigment epithelium-derived factor (PEDF) is a potent angiogenic inhibitor. The unbalanced expression ofPEDF and vascular endothelial growth factor (VEGF) may play an important role in thecourse of diabetic nephropathy. The present study is aimed to observe the expression ofserum PEDF and serum VEGF in type2diabetic patients with diabetic nephropathy,illuminate the relationship between the biomarkers with parameters associated withdiabetic nephropathy. The study is also performed to elucidate the effect of Valsartancombined Sodium Ferulate on the expression of serum PEDF and serum VEGF in patientswith diabetic nephropathy. These researches also provide new treatment for prevention ofdiabetic nephropathy.Methods90type2diabetes patients(male54, female36) with normal serum creatinine wereenrolled from The Military General Hospital of Jinan during July2010to October2011.The patients were divided into three groups according to the albumin：creatinine ratio(ACR): Normoalbuminuria group (NA), Microalbuminuria group (MA), Clinical-albumin-uria group (CA).30healthy subjects were selected as healthy control group. The patientsof MA and CA were randomly divided into two groups, the Valsartan group and theValsartan combined Sodium Ferulate group. Serum and urine collected from subjects weremeasured by Enzyme linked immunosorbant assay(ELISA). Glycosylated haemoglobin(HbA1c), triglyceride (TG), totle cholesterol (TC), serum creatinine, urinary ACR were measured. Estimated glomerular filtration rate (eGFR) was calculated by the Modificationof Diet in Renal Disease Study equation.Results1. The serum PEDF level: The serum PEDF level in MA and NA subjects wasupregulated significantly compared with the healthy control subjects（P<0.01）, and it wasincreased as diabetic nephropathy advanced. There was no significant difference amongNA and the healthy control subjects.2. The serum VEGF level: The serum VEGF level in NA, MA and CA subjects wasupregulated significantly compared with the healthy control subject（sP＜0.01or P＜0.05）,and it was increased as diabetic nephropathy advanced.3. Pearson correlation tests demonstrated significant positive correlations between theserum PEDF level and age (R=0.218，P＜0.05)、HbA1c (R=0.222，P＜0.05)、SBP(R=0.252，P＜0.05)、TC (R=0.390，P＜0.01)、TG (R=0.275，P＜0.01)、lgACR (R=0.701，P＜0.01)、Scr (R=0.410，P＜0.01)), significant negativee correlations between the serumPEDF level and eGFR (R=-0.447，P＜0.01). There were not correlations between theserum PEDF level and duration, BMI, DBP and FBG.4. Pearson correlation tests demonstrated significant positive correlations between theserum VEGF level and duration (R=0.375，P＜0.01)、HbA1c (R=0.220，P＜0.05)、SBP(R=0.311，P＜0.01)、DBP (R=0.265，P＜0.05)、TC (R=0.319，P＜0.01)、TG (R=0.427，P＜0.01)、lgACR (R=0.765，P＜0.01)、Scr (R=0.402，P＜0.01), significant negativeecorrelations between the serum PEDF level and eGFR (R=-0.401，P＜0.01). There werenot correlations between the serum PEDF level and age, BMI, and FBG.5. Pearson correlation tests demonstrated significant positive correlations between theserum PEDF.level and the serum VEGF level (R=0.565，P＜0.01).6.21days afer treatment, the lever of ACR, the serum PEDF and the serum VEGF ofpatients in the Valsartan group and the Valsartan combined Sodium Ferulate group hadsignificantly reduced (P<0.01or P＜0.05), and the Valsartan combined Sodium Ferulategroup reduced most obviously.Conclusion1. Serum PEDF and VEGF level were evaluated in type2diabetic patients withdiabetic nephropathy.2. The serum PEDF level were associated with parameters of diabetic nephropathy（HbA1c、SBP、TC、TG、ACR、Scr、eGFR）, Serum PEDF level was positively correlated with serum VEGF level.3. The serum VEGF level were associated with parameters of diabetic nephropathy（HbA1c、SBP、DBP、TC、TG、ACR、Scr、eGFR）.4. Valsartan combined Sodium Ferulate significantly decreasesd proteinuria, serumPEDF level, and serum VEGF level, the results showed Valsartan combined SodiumFerulate might play a protective role in the development and progression of diabeticnephropathy by correcting abnormal angiogenesis.5. The combinantion of Valsartan and Sodium Ferulate is more effective thanValsartan alone.