Lumbrokinase attenuates diabetic nephropathy through regulating extracellular matrix degradation in Streptozotocin-induced diabetic rats

Objective: The present study was undertaken to investigate the therapeutic effect and underlying mechanisms of lumbrokinase on diabetic nephropathy. Methods: Type I diabetes was induced in male Sprague-Dawley rats via intraperitoneal injection of Streptozotocin (STZ). Lumbrokinase was administered to the diabetic rats at a dose of 600,000 U/kg body weight by gavage. As a positive control, perindopril, an angiotensin-converting enzyme inhibitor (ACEI), was given to diabetic rats at a dose of 4 mg/kg body weight. Following 12 weeks treatment, we measured the creatinine clearance rate (Ccr), urinary albumin excretion (UAE) and kidney injury scores. In addition, the expression of collagen IV, MMP-2 and MMP-9 in renal tissue was evaluated. Results: The diabetic rats developed proteinuria, glomerulosclerosis, tubulointerstitial fibrosis and a marked increase of renal cortical collagen IV. In contrast, MMP-2 and MMP-9 were significantly reduced in the renal cortex of diabetic rats. Interestingly, lumbrokinase treatment markedly reduced the proteinuria and improved the glomerulosclerosis and tubulointerstitial fibrosis in diabetic rats. The induction of collagen IV and the down-regulation of MMP-2 and MMP-9 was significantly attenuated by lumbrokinase. All these beneficial effects of lumbrokinase were comparable to the ACEI group. Conclusion: Lumbrokinase treatment attenuated diabetic nephropathy in rats, possibly through increasing the activity of MMPs and the subsequent degradation of extracellular matrix. (C) 2013 Elsevier Ireland Ltd. All rights reserved.