Effects Of Rapamycin On The Barrier To Penetration Of Glomerulus Of Adriamycin Induced Nephrotic Syndrome In Rats

Minimal chang nephrotic syndrome(MCNS) was investigative task of all the world, adriamycin(ADR) induced nephrotic syndrome(ANS) in rats was the known animal model of MCNS. There were some facters that possiblely caused MCNS, such as inherent cause, the abnormality of CL that viral infection led to, peroxidize injury, cellular immunity. The injury of the barrier to penetration of glomerulus were the most important facter. The main drug was glucocorticoid and immunity inhibitor, besides antioxidant, ACEI and some Chinese traditional medicine. The neotype immunity inhibitors had the better effect of treatment, and little side effect, such as FK506, rapamycin. At present, it was considered that the rate of efficiency was 75%～90% by use of CsA in MCNS,but in the course of treatment there were often renal injury, i.e. renal desmohemoblast lesion. Rapamycin was a high-effect and low-toxicant immunity inhibitor,and combined with FKBP12, developed immunity inhibitory action. Now I had not checked the reports about Effects of rapamycin on the barrier to penetration of glomerulus of adriamycin induced nephrotic syndrome in rats. One Japanese scholar reported FK506 could cut down the amount of 24h urine protein of rats, alleviated the fusion of foot processes,reduced the number of missed anionic sites in glomerular basement membranes. Rapamycin and FK506 had the same receptor and similar structure.Objective:To investigate effects of rapamycin on adriamycin induced nephrotic syndrome in rats. Set up induced nephrotic syndrome in rats, process different medicines and groups control research, observe the rats' changs of blood urea nitrogen(BUN), cholesterol(Tc), albumin(ALB),24h urine protein and the number of anionic sites in glomerular basement membranes,as well as renal histologic changes in different dosage of rapamycin and compare with the CsA group,and provide the basis for rapamycin applying to the clinical treatment of MCNS.Methods: Experimental animals are male healthy SD rats, about 220g.experimental drugs include adriamycin, rapamycin, CsA.Setting up the rat models of MCNS:In non-narcotism,ADR induced NS rat models are made by a single injection of 5mg/kg ADR via tail vein, and the rats of health control group are given a single injection of 5mg/kg physiological saline.Groups:there are 5 groups,8 rats in every group.A group is normol control group; B group is model control group; C group is CsA group (10mg/kg?d); D group is rapamycin group 1(3mg/kg?d); E group is rapamycin group 2(6mg/kg?d).The index: It was observed in 40 ADR induced NS rat models made by a single injection of ADR via tail vein,that the changs of blood urea nitrogen, cholesterol, albumin, 24h urine protein and the number of anionic sites in glomerular basement membranes, as well as renal histologic changes. after 8 weeks, different therapies were compared in 5 groups,normol control, model comtrol,CSA therapy, and RAP(3mg/kg?d) therapy, RAP(6mg/kg?d)Results:1.The setting up of rat models of MCNS: After 14 days, the rats of B group had a great deal of proteinuria(120.18±51.34mg/24h),and in about 5-6 weeks reach the peak(456.94±68.66mg/24h).At the same time, hyp- albuminemia and hyperlipemia come forth. The histology of B group rats' kidney: under microscope ,glomeruli of kidney are normal；under electric mirror, foot processes fused.2.After 8 weeks, the changs of blood urea nitrogen, cholesterol, albumin, 24h urine protein and the number of anionic sites in glomerular basement membranes,as well as renal histologic changes were compared in 5 groups, i.e. normol control group,model comtrol group,CSA therapy group, and RAP(3mg/kg?d) therapy group, RAP(6mg/kg?d) therapy group.3.The histological change of Each group: A group:they are normal under microscope and electric mirror. B group: under naked eyes,large white kidney emerges; under electric mirror, foot processes fused widely . C group: under electric mirror, foot processes fused partly. D, E group: under microscope, glomeruli of kidney lo...