[Study on mechanism of Shenle and Fragmin in preventing and treating glomerulosclerosis in rats].
OBJECTIVE
To study the effects of Shenle and Fragmin on the degradation of extracellular matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase-1 (TIMP-1) in the remnant kidneys of 5/6 nephrectomized rats treated with Shenle and Fragmin.


METHODS
The model of focal and segmental glomerulosclerosis was made by 5/6 nephrectomy in Wistar rats. After being treated with Shenle (4 g.kg-1.d-1) or Fragmin (1000 IU.kg-1.d-1) for 20 weeks, the blood pressure, proteinuria, serum creatinine, lipids, renal pathological change of remnant kidney of the model animals were examined, and the mRNA expression of MMP-9, TIMP-1 and type IV collagen in the remnant kidney were also detected.


RESULTS
Shenle and Fragmin could significantly reduce the blood pressure, proteinuria, serum creatinine and lipids, alleviate the pathologic change of kidney tissue, decrease the type IV collagen, MMP-9 deposition. Shenle and Fragmin down-regulated the mRNA expression of MMP-9 by 30.0% and 28.5% and TIMP-1 expression by 59.3% and 55.0% in the remnant kidney of the 5/6 nephrectomized rats respectively.


CONCLUSIONS
Shenle and Fragmin might ameliorate glomerulosclerosis through modulating MMP-9/TIMP-1 gene expression, alleviate the abnormal metabolism and accumulation, promote extracellular matrix degradation in glomeruli remodeling, it might be the important mechanism of Shenle and Fragmin in treating glomerulosclerosis.
Wang
W
W
Nephrology Department, General Hospital of PLA, Beijing 100853.
Chen
X
X
Ye
Y
Y
D000818:Animals; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D017985:Dalteparin / Q000627:therapeutic use*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000517:prevention & control*; D006629:Hirudins; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009392:Nephrectomy; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics
D004365:Drugs, Chinese Herbal; D006629:Hirudins; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D020780:Matrix Metalloproteinase 9; D017985:Dalteparin