| Background and objective Diabetic nephropathy (DN) is one of the most common chronic complications of diabetes mellitus and the major cause end-stage renal disease(ESRD). An interaction of metabolic and hemodynamic factors has been considered a traditional aspect involved in the development of renal lesions in patients with type 1 or type 2 diabetes. However, the recent study in vivo and in vitro has demonstrated that inflammation is an important cause in chronic progressive renal disease in diabetic patients. It widely accepted for the time being that therapeutic principles for DN are as follows: the control of hyperglycemia, blood pressure and diet as well as renal function protection. Up to now, it reported is less that diabetic nephropathy treatment with immunosuppressive. Mycophenolate mofetil(MMF) is a mew immune suppressor. Besides highly selective inhibition of lymphocyte proliferation, it could also inhibit the proliferation of mesangial cells and monocytes, reduce expression of cell adhesion molecules and reduce deposition and accumulation of ECM. Therefore, this study through the diabetic rats treatment with MMF, investigating the effect of MMF on the expression of transforming growth factor- 1(TGF- 1) and osteopontin(OPN) in the kidney of diabetic nephropathy rat, and to provide experimental evidence for the application of immunosuppressive drugs in treatment of diabetic nephropathy.Methods SD rats were randomly divided into normal controls(group NC) diabeticgroup(group DM) and MMF treatment group(group MMF) Diabetes was induced by peritoneal injection of STZ. Rats of group MMF were given MMF l5mg-kg-d while group DM given the same amount of NS Observing the change of blood glucose 24hours urinary protein, Serum creatinine, Urea nitrogen , the kidney weight-body weight blood lipid Sacrificed the rats after 8 week and observing change of histology and expression of TGF- 1 and OPN.Results 1. The changes of blood glucose, kidney weight/body weight(KW/BW) and 24 hours urinary protein in each group: Blood glucose, kidney weight/body weight(KW/BW) blood lipid and 24 hours urinary protein increased significantly in DM model group and MMF treatment group compared with control group There was significant between DM model group and MMF treatment group. Correlation analysis showed that the change of blood lipid was positively correlated with blood glucose.2. Pathological changes: At the end of the 8th week, glomerular lesions in rats were characterized by thickening of the basement membrane, mesangial expansion, sclerosis and interstitial fibrosis. The glomerulosclerosis and interstitial fibrosis in diabetic rats increased significantly compared with that of control. Treatment with MMF could significantly reduce glomerulosclerosis in diabetic rats. 3. The changes of high sensitive C-reactive protein(Hs-CRP) in each group: Hs-CRP increased significantly in DN model group and MMF treatment group compared with control group There was significant between DM model group and MMF treatment group. 4. Immunohistochemistry: The levels of TGF- 1 and OPN were increased both in glomerular and tubulointerstitium in group DM and MMF compared with group NC There is a significant decrease of MMF treatment group compared with the DM group Levels of the TGF- 1 and OPN expression had positive correlations with UAER and KW/BWConclusion The expression of TGF- 1 and OPN in renal tissue were significantly increased in diabetic rat, MMF suppress the overproduction of TGF- 1 and OPN in the kidney of diabetic nephropathy rat, reduce KW/BW and 24 hours urinary proteinReduce the glomerular and tubular sclerosis and fibrosis, MMF can prevent the progression of diabetic nephropathy. |
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