| The Effects of Probucol on Oxidative Stress and Expression of VEGF in the Kidneys in A11oxan-Induced Diabetic NephropathyRatsAims: Probucol has an antioxidant property. This study is toanalyze the effects of antioxidant on oxidative stress and expression of VEGF in the kidneys in diabetic nephropathy rats and discuss the mechanism of renoprotection of probucol.Methods: 60 Sprague-Dawley male rats were randomly divided intofour groups: group A (normal control, 8 rats);B (unilateral renal blood vessel ligation, 8 rats);C (unilateral renal blood vessel ligation and diabetes, 22 rats) and D (unilateral renal blood vessel ligation and diabetes and probucol administrated, 22 rats). Right renal blood vessles of the rats in group B, C and D were ligated. After one week the diabetes modol were established by intravenous injection of alloxan, using the single dose of 50 mg/kg in group C and D. Probucol was administrated orally through intragastric tube at the dose of 170mg/(kg. d) in group D for three weeks after the diabetes were successfully induced. 24h urine was collected before the rats were sacrificed and 24h urinary microalbumin was examined. When all rats were killed the left kidneys were harvested and weighted to calculate the kidney hypertrophy index(LK/BW). The blood samples were collected to determined BG, BUN, Cr, TC, TG, LDL, VLDL, HDL and MDA. The activities of serum SOD, blood CAT and GSH-PX were measured. HE staining was used to evaluate the renal pathological changes by light microscope. VEGF was detected with immunohistochemical analysis. All data were analyzed using the SPSS 12. 0 PC program for windows.Results: The BG was significantly increased and the weight wassignificantly decreased in ALX-induced DM rats of group C and D (P<0. 001). Compared with group A, the levels of MDA and GSH-PX increased and the ratio of SOD/MDA decreased in group B (P<0.05). The activities of CAT and SOD had no significant difference between group A and B (P>0. 05). Compared with group A and B, the serum MDA and the activity of blood GSH-PX were significantly increased (P<0. 05), the ratio of SOD/MDA and the level of CAT were significantly decreased (P<0.05) in group C and D. The MDA of group C was significantly higher than group D (P<0. 05). The ratio of SOD/MDA and the activity of CAT in group C were significantly lower than group D (P<0. 05). 24h UMA was significantly higher in group C and D than group A (P<0.05). Compared with group A, the kidney hypertrophy index (LK/BW) increased in group B (P<0.05). The ratio of LK/BW was significantly higher in group C and D than group A and B (P<0. 05). The ratio of LK/BW had no significant difference between group C and D (P>0.05). The expression of renal VEGF was analyzed by IHC. Compared with group A, the renal mean optical density and area density of VEGF weresignificantly increased in group B, C and D (P<0. 05). The renal mean optical density and area density of VEGF were significantly higher in group C than group D and B (P<0. 05). The tubular area density of VEGF in group D was significantly higher than group B (P<0. 05). The gloraerular mean optical density and area density, the tubular mean optical density had no significant difference between group D and B (P>0.05). BG, LDL, UMA, LK/BW, BUN, Cr, the glomerular and tubular mean optical density and area density had a significant positive correlation with MDA (P<0.01) and had a significant negative correlation with SOD and SOD/MDA (P<0. 01). The glomerular mean optical density and tubular area density had a significant positive correlation with BG, UMA, LDL, LK/BW, BUN and CrConclusion: Our studies revealed that the diabetic nephropathyrats modol could be successfully established by alloxan after the ligation of unilateral renal blood vessel. Probucol may improve the activity of antioxidant enzyme, reduce the content of oxidant substance and the level of renal VEGF expression. Probucol may provide a renoprotective effect. Oxidative stress and VEGF could play a crucial role in the development and progression of diabetic nephropathy and antioxidant treatment could be a potential therapeutic procedure for diabetic nephropathy. |
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