Expression and Significance of Matrix Metalloproteinase and Tissue Inhibitor of Metalloproteinase-1 in Rats with Glomerular Sclerosis

Objective To investigate expression and significance of matrix metalloproteinase-2(MMP-2),MMP-9 and tissue inhibitor of metalloproteinase-1(TIMP-1) in rats with glomerular sclerosis made by doxorubicin.Methods Forty Wistar male rats(8-week-old) were randomly assigned into 2 groups:sham operated and model groups.Rats in model group were nephrectomized after anesthesia and injected with adriamycin(5 mg/kg) after 1 week.Rats in sham operated group was subjected to sham operation and injected with normal saline after 1 week through the tail vein.All rats were killed in the 12th week.Immuno-histochemistry was performed on renal tissue to detect Collagen Ⅳ(Col-Ⅳ),fibronectin(FN),MMP-2,-9 and TIMP-1.Results Immunohistochemistry staining indicated that expressions of MMP-2,-9 in model group decreased significantly compared to sham operated group(Pa0.01).To the contrast,the expression of Col-Ⅳ,FN and TIMP-1 in model group increased(Pa0.01).The ratio of TIMP-1/MMP-2 and TIMP-1/MMP-9 both increased(Pa0.01).There were positive relative among TIMP-1,TIMP-1/MMP-9,TIMP-1/MMP-2 and glomerular sclerosis index(GSI)(Pa0.01).To the contrast,there were negative correlation among MMP-2,-9 and GSI(Pa0.01).Conclusion The disproportion of TIMP-1/MMP-2 and TIMP-1/MMP-9,which resulted in the decreased degradation of extracellular matrix (ECM),may contribute to the development of glomerular sclerosis.