Effects Of Mycophenolate Mofetil On Adriamycin Nephropathy

Objective Proteinuria is a important factor in the progress of kidney disease, the abnormal structure and function of podocyte protein molecules is crucial to proteinuria. Renal fibrosis is the common pathway of ESRD, CTGF acts as a crucial factor in the process. We detected the changes of nephrin and connective tissue growth factor(CTGF) in adriamycin nephropathy rats, studied the effects of mycophenolate mofetil on minimal change disease and Focal segmental glomerulosclerosis , investigated its possible mechanisms. Methods1. 22 SD rats were randomly divided into three groups: control group(CG, n=6), adriamycin model group(AG, n=8), MMF treated group(TG, n=8). Rats in MG and TG were given adriamycin 7.5mg ? kg^-1 through vena caudalis. At the same time, an equal volume of normal saline was given to the rats in CG by the same method. The rats in TG received MMF 20mg? kg^-1?d^-1 by daily gastric gavage from the second day. Urinary protein excretion of each rat were measured at the day before adriamycin injection, the 14th day and the 28th day after adriamycin injection. Six rats of each group were killed at the 28th day. Serum urea nitrogen, creatinine, cholesterol , triglyceride and albumin were measured at the end of the study. Immunohistochemistry and western blot were used to examine the expression of nephrin.2. 24 SD rats were randomly divided into three groups: control group(CG, n=8), FSGS model group(FG, n=8), MMF treated group(TG, n=8). Rats in MG and TG were given adriamycin 7.5mg ? kg^-1 through vena caudalis. At the same time, an equal volume of normal saline was given to the rats in CG by the same method. The rats in TG received MMF 20mg? kg^-1? d^-1 by daily gastric gavage from the 6th week. Renal pathological changes were evaluated at the 10th week. The expression of connective tissue growth factor(CTGF) were analyzed by immunohistochemistry and western blot. Results1. 1.1 The urinary protein excretion of AG at 28th day was the highest. Serum albumin decreased markedly at the 14th day(p<0.01), Cholesterol and triglyceride increased significantly at the 14th day. Proteinuria, serum cholesterol and triglyceride of the rats in TG were lower than those of the rats in AG at the 28th day. Serum albumin level were higher than those of AG(p<0.01).1.2 The results of Immunohistochemistry and western blot indicated the expression of nephrin of AG rats decreased at 14th day compared to those in CG (p<0.01 ), the expression of nephrin of TG rats are higher than those of AG rats(p<0.01).2. The proliferation of the mesangial cells and the accumulation of the extracellular matrix in FG were severe than in CG, the expression of CTGF protein increased significantly (P<0.05); the proliferation of the TG rats wereameliorated, the expression of CTGF decreased markedly in TG rats(p<0.05)Conclusions 1 MMF can ameliorate the kidney injury of minimal changedisease, it may be related to the increase of nephrin protein.2. MMF can ameliorate kidney interstitial fibrosis, the effect is related todecrease of CTGF expression.