Effect Of MMF On TGF-β1 And ET-1 Expression In Kidney Of STZ Induced Diabetic Juvenile Rats

Objectives:To research the expressions of Transforming growth factor-β1(TGF-β1)and endothelin-1(ET-1) in kidney tissue of Juvenile rats by preparing the animal models of T1 DM caused by streptozotocin(STZ) and adding Mycophenolate mofetil.Combined with the change of urinary protein, renal function and renal index, explore the relationship between TGF-β1、ET-1 and kidney injury caused by diabetes. Explore the protective effects of MMF in kidney tissue of diabetic rats.Method:1.The 30 male SD rats,adaptive feeding one week,were randomly divided into normal control group( 10 rats), the experimental group(20 rats).Streptozotocin(STZ), at a dose of 65mg/kg body weight dissolved in citrate buffer, was injected intraperitoneally to induce diabetes. Seven days after STZ injection, blood glucose level was checked using the glucometer. The animals with a blood glucose level of more than 16.7mmol/L were considered diabetic and included in the study. The animals were segregated into three groups with ten animals each. The groups included were normal control rats(N), STZ induced diabetic rats(D), diabetic rats treated with MMF at a dose of 10 mg/kg?1day by fill the stomach for 4 weeks(M).The rats of group N and D were received the same amount solvent for 4 weeks.2.Rats in each group were dealed with in four week. Collected urine samples with metabolic cages method. Collected blood and prepared Renal biopsy. Blood glucose level was checked using the glucometer. Serum creatinine,urea nitrogen,and Urinary protein concentration were detected by Automatic biochemical analyzer.Quatily of kidney and rat were tested by Electronic balance. Renal pathological changes were observed under light microscope(400-fold). TGF-β1,ET-1 was detected by immunohistochemistry.Result:1.Random blood glucose of group M and D were obviously increased than group N(P<0.01), but there were no significant difference between group M and D(P > 0.05). The KWI of group M and D were higher than group N(P < 0.01).Moreover, the KWI of group R were lower than the D group(P<0.01).2. Scr, BUN and 24-hour urine protein of group M and D were obviously increased than group N(P<0.01), the Scr、BUN of group M were lower than the D group,but there were no significant difference between group M and D(P>0.05),The 24-hour urine protein of group M were lower than the D group(P<0.01).3.Compare with group N, the expression of TGF-β1、ET-1 of group M and D were obviously increased(P<0.01), group M were obviously decreased than group D(P<0.01).4.HE staining: Diabetic model group rats showed proliferation of Glomerular and mesangial cells,, basement membrane thickening, swelling renal tubule, luminal stenosis or occlusion. But the Pathological changes of group M were significantly reduced compared with group D.5.In group D,KWI and 24-hour urine protein are positively associated with the expression of TGF-β1( r=0.992, 0.992). In group M,KWI and 24-hour urine protein are positively associated with the expression of TGF-β1( r=0.996, 0.980).6.In group D or M,the expression of TGF-β1 and ET- 1 showed a positive correlation(r=0.985,0.994).Conclusion:1.MMF has a significant protective effect to the kidney of STZ-induced diabetic juvenile rats. The therapeutic potential of MMF in the treatment of diabetic nephropathy as shown by the significant reduction of KWI and proteinuria.2.MMF reduce TGF-β1 expression and inhibit inhibition of inflammation in kidney of STZ-induced diabetic juvenile rats, and then reduce the accumulation of extracellular matrix,slow down the process of renal fibrosis.3.MMF reduce ET-1 expression and inhibit inhibition of inflammation in kidney of STZ-induced diabetic juvenile rats, increased extracellular matrix degradation,alleviate kidney inflammation and endothelial dysfunction...