title: Lumbrokinase attenuates diabetic nephropathy through regulating extracellular matrix degradation in Streptozotocin-induced diabetic rats.
abstract: 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.
  
  
  CONCLUSIONS
  Lumbrokinase treatment attenuated diabetic nephropathy in rats, possibly through increasing the activity of MMPs and the subsequent degradation of extracellular matrix.
authors: Department of Nephrology, Shenzhen Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, China.
authors: Huili
authors: H
authors: Sun
authors: Na
authors: N
authors: Ge
authors: Mumin
authors: M
authors: Shao
authors: Xiaoyan
authors: X
authors: Cheng
authors: Yue
authors: Y
authors: Li
authors: Shunmin
authors: S
authors: Li
authors: Jiangang
authors: J
authors: Shen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D024141:Collagen Type IV / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D010450:Endopeptidases / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000473:pathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D024141:Collagen Type IV; D010450:Endopeptidases; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; C083421:lumbrokinase; D003401:Creatine