Role of matrix metalloproteinase 9 in the pathogenesis of diabetic nephropathy in rats

Abstract

Objective To explore the role of matrix metalloproteinase 9(MMP-9) in the development of diabetic nephropathy(DN).Methods Healthy female rats were randomly divided into diabetic group and control group. Diabetic rat model was established by injection of STZ. Four and eight weeks after rats were sacrificed, zymography was used to detected the activity of renal MMP-9. Immunohistochemistry was used to examine the expressions of renal MMP-9, type Ⅳ collagen and laminin. Correlation of MMP-9 expression and activity with type Ⅳ collagen and laminin was performed. Results MMP-9 expression was positive in glomerular and tubular cells of control group (week 4:26.63%±2.91%, week 8:29.86%±0.89%) , while above MMP-9 expression was down-regulated significantly in diabetic group (week 4:16.11%±2.86% , week 8:13.14%.±2.68%).The activity of MMP-9 decreased significantly in diabetic group compared to control group as well(control group week 4:110.47±7.12, week 8:111.50±6.95; diabetic group week 4:82.74±10.92, week 8:80.05±12.83)(all P＜0.0l). The expression and activity of MMP-9 were negatively correlated with type Ⅳ collagen (r=-0.852, -0.795, all P＜0.01) and laminin expression (r=-0.897, -0.832, all P＜0.01). Conclusion MMP-9 expression and activity decrease in renal tissues of diabetic rats, which may play an important role in the pathogenesis of diabetic nephropathy. Key words: Diabetic nephropathies; Matrix metalloproteinase 9; Collagen type Ⅳ; Laminin; Rats