| Objective: Diabetic nephropathy is one of the main causes of renal end-stage disease. It is characterized by excessive accumulation of extracellular matrix (ECM)in the kidney, in additionally transforming growth factor- β1(TGF-β1) is a critical promoter that mediates the excessive production of ECM in the kidney. Diabetic nephropathy is associated with progressive kidney macrophage accumulation. Monocyte chemo- attractant protein-1(MCP-1) and intercellular adhesion molecule-1(ICAM-1) facilitate macrophage recruitment in the kidney and participate renal fibrosis. Oxidative stress stimulates TGF- β1, MCP-1 and ICAM-1 production, and plays a role in the excessive accumulation of ECM. Probucol is a kind of antioxidative and lipid-lowering agent ,and the aim of this study is to observe the effects of probucol on the renal expression of TGF- β1, MCP-1 and ICAM-1 and to investigate its renoprotective effects .Methods: 60 SD male rats were randomly divided into 4 groups, which were group A (normal control group,8 rats), B (right renal blood vessel-ligated control group, 8 rats), C (diabetes group, 22 rats), and D (diabetes and probucol-treated group, 22 rats).The right renal blood vessels of group B, C and D were ligated. Diabetes was established in rats of group C and D by intravenous injection of alloxan at dose of 50mg.kg-1. After 72 hours, measured random blood glucose, and the one whose blood glucose was above 16.7mmol/L was enlisted. The rats of probucol-treated group were treated probucol 170mg.kg-1 by gavage every day for 3weeks. Before the rats were sacrificed, collected 24 hours' urine for measurement of urine albumin excretion rate(UAER), then killed the rats, gathered blood from femoral artery immediately, and measured their serum creatinine(Scr), blood urea nitrogen(BUN), triglyceride (TG), total cholesterol(TC), low-density lipoprotein(LDL), very-low- density lipoprotein(VLDL) and high-density lipoprotein (HDL). After that, the left kidney and the pancreas were removed , and the kidney was weighed to calculate the ratio of kidney weight to body weight (KW/BW). Put the kidney and the pancreas into 10% formalin to be fixed and made paraffinslices. Observed the pathological changes of the kidney and the pancreas , and studied the expression of TGF- P 1 , MCP-1 and ICAM-1 in the kidney with immuno-histochemical technique and computer image-analyzing instrument. The data were analyzed by SPSS system.Results: (l)Body weight and blood glucose: the weight of group C and D was separately significantly lower than that of group A and B (P<0.05), and the weight of group D was significantly higher than that of group C (P<0.05). Compared with group A and B, the level of blood glucose of group C and D was significantly higher(P<0.05), and it has no significant difference between group C and D (P>0.05). (2) Blood lipid: There was no significant difference of TG, TC, HDL and VLDL in 4 groups(P>0.05). the level of the LDLof group D was significantly lower than that of group C (P<0.05). (3)BUN and Scr: Compared with group A, B and D, the level of BUN and Scr of group C was significantly higher(P<0.05). The level of Scr of group D was significantly higher than that of group A and B (P<0.05), but there was no significant difference of level of BUN among group A, B and D (P>0.05). There was no significant difference between the levels of BUN and Scr of group A and those ofgroup B (P>0.05). (4) urine albumin excretion rate and the ratio of kidney weight to body weight: urine albumin excretion rate and KW/BW of group C and D were separately significantly higher than those of group A and B (P<0.05), and urine albumin excretion rate of group D was significantly lower than that of group C (P<0.05), but there was no significant difference between KW/BW of group D and that of group C (P>0.05). KW/BW of group B was significantly higher than that of group A, but there was no significant difference between jirine albumin excretion rate of group A and that of group B. (5) Expression of TGF- P 1, MCP-1 and ICAM-1 in the kidney: Expression of TGF- 3 1, MCP-1 and ICAM-1 in group A and B in renal tubular was low, and it significantly rose in group C (P<0.05), and expression of TGF- P 1, MCP-1 and ICAM-1 in group D was significantly lower than that of group C (P<0.05), but significantly higher than that of group A and B (P<0.05). (6)Correlation analysis:expression of TGF- P 1 , MCP-1 and ICAM-1 in the kidney had positive correlation with blood glucose, LDL, urine albumin excretion rate, KW/BW, BUN, and Scr (P<0.05).Conclusion: In alloxan-induced diabetes rats, we demonstrate that expression of TGF- P 1 , MCP-1 and ICAM-1 in the kidney rise and probucol can decrease expression of TGF- 3 1, MCP-1 and ICAM-1 in the kidney and has significant renoprotective effects.
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