Hepatocyte Growth Factor And Transforming Growth Factor-β1 May Play An Important Role In Nephrotoxic Serum Nephritis And Are Affected By Mycophenolate Mofetil And Leflunomide Effect In Rats

Objective To investigate the role of hepatocyte growth factor(HGF) and transforming growth factorβ1(TGF-β1) in rats with nephrotoxic serum nephritis, and the influence of mycophenolate mofetil(MMF) and leflunomide(LEF) on them. Methods Renal cortex homogenate of male's Sprague-Dawley rats was mixed with complete Freund's adjuvant. New Zealang white rabbits were immunized with the mixture. After several immunization, rabbits produce rabbit anti-rat nephrotoxic serum. SD rats were randomly divided into control group, model group, MMF treating group, LEF treating group,10 rats in each group. Rats in model group, MMF treating group, LEF treating group were pre-immunized with mixed liquor of normal rabbits and complete Freund's adjuvant respectively. At fifth day, nephrotoxic serum was injected into tail veins of rats (in term of pre-trial , dose is 4ml/kg), control group rats received same dose normal rabbits IgG into tail veins. After six hours of injection, MMF treating group and LEF treating group administer MMF 20mg/(kg·d) and LEF 5mg/(kg·d) by gavage respectively. Rats of control group and model group administer same dose dissolvent every day. Two weeks later, rats were sacrificed,serum total protein(TP), serum albumin(ALB) ,24h urinary protein,serum creatinine (Scr), blood urea nitrogen(BUN) were measured; morphological change of renal section were observed; the expression of HGF and TGF-β1 of glomeruli was determined by immunohistochemistry method. Results After injection nephrotoxic serum, Tp and ALB in model group rats obviously decreased(P<0.01), the level of 24h urinary protein, Scr, BUN were extremely increased(P<0.01), glomerular hypercellularity, crescent formatio(nP<0.01). Amount of glomerular cell and crescent formation of MMF treating group and LEF treating group were significantly reduced compared with model group(P<0.01), but higher than control group(P<0.01). TP and ALB of MMF treating group and LEF treating group were increased in contrast with model group(P<0.01).but lower than control group (P<0.01). The level of 24h urinary protein, Scr, BUN of MMF treating group and LEF treating group extremely lower than model group(P<0.01),while higher than control group(P<0.01). Positive index of HG of MMF treating group and LEF treating group were remarkably added compared with control group and model group(P<0.01). Positive index of TGF-β1 of control group, MMF treating group and LEF treating group were significantly decreased in contrast with model group(P<0.01). Positive index of TGF-β1 of MMF treating group higher than LEF treating group. Conclusions MMF and LEF can ameliorate glomerular hypercellularity and crescent formation of rats with nephrotoxic serum nephritis,alleviate renal injury,improve renal function. This suggest that potentiation of HGF expression and repression of TGF-β1 express may be beneficial to alleviate renal injury, crescent formation. HGF is renoprotective factor.