| [Backgroud and Objective] The severity of tubulointerstitial fibrosis has long been considered as the crucial determinant in progressive renal injury and long term prognosis in both human and experimental glomurulonephritis .How to impede interstitial fibrosis and limit the progression of chronic renal diseases towards end stage renal disease(ESRD) become an new focus in this field. Inflammation of the tubulointertitial compartment, leading to fibrosis, is a major factor in the progressive loss of renal function in patients with a wide variety of kidney diseases.A contributing factor to renal fibrosis is the proliferation- of fibroblasts in the interstitium and epithelial-mesenchymal transdifferentiation.Myofibrolast(MyoF) plays a crucial role in renal fibrosis .Excessive extracellular matrix(ECM) produced by MyoF ultimately reduces the filtration surface area of the glomeruli and leads to renal failure.Mycophenolate mofetil (MMF)is a highly specific immunosuppressor and is the morpholinoethyl ester of mycophenolic acid (MPA), which is released after oral administration and constitutes the actually active compoundand. MPA arrests lymphocyte proliferation by inhibiting inosine monophosphate dehydrogenase (IMPDH), a crucial enzyme in the de novo pathway of GTP synthesis. Also it can reduce inflammation cells infiltration and expression of ICAM in endothelial and tubular epithelial cells in rat remnant kidney and UUO model kidney. Interestingly,MMF is an immunosuppressive drug that is also known to have an effect on cells outside immune system.It is reported that MMF inhibit proliferation of mesangial cell and fibroblast cell and decrease deposition ofextracellar matrix,so MMF has renoproctective effects in a non-immune renal disease model .Therefore we decided to investigate whether MMF has additional effects on UUO rats treated with losartan.[ Methods ]Thirty female Sprague Dawley rats obtained from the Animal Center of Zhengzhou University (weighting 200?0g)were used in this study.The rats were randomly divided into 5 groups:sham operated group(n=6),UUO group (n=6),UUO+MMF(n=6,25mg.kg-1.d-1);UUO+ARB(n=6,50mg.kg-1.d-1);MMF+ARB( n=6). Obstructed kidneys were harvested 14 days after operation. Systolic blood pressure was measured using the tail-cuff method .The samples of blood and the urine of 24 hours were collected to detect the concentration of serum creatinine, the quantity of urinary protein and creatinine . The paraffin insections(3 m)of the kidney were stained with HE and MASSON for collagen identification.The expression of TGF-1, type III collagen , a-SMA were evaluated by SP kit . Data were expressed as x s and were compared among groups by one way analysis of variance .[Results] 1. Blood pressure and biochemistry test:In comparison with shame operation group, there was no significant difference in the blood "pressure, the quantity of urinary protein of 24 hours, the clearance of creatinine rate of different time rats among UUO group and other treatment groups(P>0.05) .2. In comparison with shame operation group, HE and Masson staining showed that there was more collagen deposition ,fibroblast proliferationand diffused lymphocyte infiltration in the interstitium of 14d UUO rats.The severity of interstitial fibrosis was significant alleviated by MMF or ARB treatment, the more protection with MMF+ARB(P<0.05) 3.The immunobiochemistry change of the UUO kidneys. (1)The expression of a-SMA in tubulointerstitium: In comparison with shame operation group , The expression of a-SMA of UUO and all treatment groups (P<0.05).All treatment groups were significantly decreased its expression in comparison with UUO group in the same time group,as well as the more protection with MMF+ARB (P<0.05).There was no significant difference between MMF group and Losartangroup (P<0.05).(2)The expression of TGF-6: in tubulointerstitium: In comparison with shame operation group , The expression of TGF-1 of UUO and all treatment groups (P<0.05).All treatment groups were significantly decreased its expression in comparison... |
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