Renoprotective effect of Bortezomib on adriamycin-induced nephropathy in rats

Objective To investigate the effect of Bortezomib on adriamycin-induced nephropathy in rats. Methods Sixteen male SD rats were randomly divided into normal control group (n =4) and adriamycin-induced nephropathy group (n = 12). Four weeks after model establishment by intravenous injection of adriamycin, rats in adriamycin-induced nephropathy group were divided into model group, Bortezomib 30 μg/kg treatment group and Bortezomib 60 μg/kg treatment group, with 4 rats in each group. The blood and urine parameters including serum creatinine (SCr), blood urea nitrogen (BUN), albumin (Alb) and urinary albumin to creatinine ratio (ACR) in each group were detected. Eight weeks after model establishment, rats were sacrificed after blood sampling from heart, and renal tissues were obtained. The pathological changes of tubulointerstitium and glomerulus were observed with PAS and Masson staining, and the expression of a- smooth muscle actin (α-SMA), collagen type I (Col I) and collagen type III (Col III) in renal tissues was detected by immunohistochemistry. Results Compared with normal control group, ACR in model group, Bortezomib 30 μg/kg treatment group and Bortezomib 60 μg/kg treatment group were significantly higher2 weeks after model establishment. Eight weeks after model establishment, serum SCr, BUN and ACR were significantly lower, and Alb was significantly higher in Bortezomib 30 μg/kg treatment group and Bortezomib 60 μg/kg treatment group than in model group. For tubulointerstitium injury index, glomerulosclerosis score, percent of collagen deposition area and expression of ot-SMA, Col I and Col IH in renal tissues, model group, Bortezomib 30 μg/kg treatment group and Bortezomib 60 μg/kg treatment group were significantly higher than normal control group, Bortezomib 30 μg/kg treatment group and Bortezomib 60 μg/kg treatment group were significantly lower than model group, and the treatment effect was most significant in Bortezomib 60 μg/kg treatment group. Conclusion Bortezomib could significantly ameliorate fibrosis of adriamycin-induced nephropathy, and prevent the progression of adriamycin-induced nephropathy in rats.