Abstract:

Objective  To study the dynamic changes of collagen metabolism and MMP-2/TIMP-2 expressions in hearts of diabetic rats. Methods   Wistar rats were randomly divided into four groups: 4-week normal controls, 4-week diabetic rats, 12-week normal controls, and 12-week diabetic rats. The diabetic rats were induced by injecting streptozotocin(STZ, 60mg/kg). The collagen content, serum MMP-2/TIMP-2 levels, cardiac activity, mRNA and protein expressions of MMP-2/TIMP-2were determined. Results  The collagen contents were increased in diabetic rat hearts (P＜0.01). The activity, mRNA expression and protein level of MMP-2 were decreased (P＜0.01 except P＜0.05 in MMP-2 activity between 4-week diabetic rats vs normal controls) while the serum level and mRNA expression of TIMP-2 were increased (P＜0.05, P＜0.01) in diabetic hearts. The serum MMP-2 level and cardiac TIMP-2 protein level were slightly increased at 4 weeks (P＞0.05) but markedly at 12 weeks (P＜0.05, P＜0.01) in diabetic rats. The cardiac MMP-2/TIMP-2content was positively related to the serum MMP-2/TIMP-2levels (r=0.565, P＜0.01; r=0.415, P＜0.05) and gene and protein expressions of TIMP-2 (r=0.609, 0.620; P＜0.01) while it was negatively related  to activity, gene and protein expressions of MMP-2 (r=-0.797, -0.704, -0.613;  P＜0.01).  Conclusion    Imbalance of MMP-2/TIMP-2 might participate in the development of diabetic cardiomyopathy. Serum MMP-2/TIMP-2might be potential markers for early diagnosis of diabetic cardiomyopathy.

Key words: Diabetic cardiomyopathy; Collagen; Matrix metalloproteinases; Tissue inhibitors of metalloproteinases; Rats, Wistar