Effect of Irbesartan on AGEs-RAGE and MMPs systems in rat type 2 diabetes myocardial-fibrosis model

摘要

To investigate the effect of Irbesartan on the changes of myocardial advanced glycation end products and their receptor (AGEs-RAGE), and matrix metalloproteinases (MMPs) systems in rat type 2 diabetes myocardial fibrosis model. All male Sprague-Dwaley rats were randomly divided into four groups: control (CON), high glucose and high-caloric diet (HC), type 2 diabetes (T2DM) and Irbesartan + T2DM (Ir+T2DM) groups. At 12th week, the fasting blood glucose (FBG) and fasting serum insulin (FINS) levels, insulin resistance index (IRI), insulin sensitivity index (ISI), body weight (BW), the ratio of heart weight/body weight (H/B), left ventricular weight index (LVWI), and cardiac col I, col III contents, plasma MMP-2, MMP-9 levels were evaluated. The protein expressions of col I, AGE, RAGE, MMP-2, MMP-14, and TIMP-2 were analyzed by Western blot. In the T2DM group, FBG, H/B, LVWI, IRI were increased (P < 0.01), while FINS, BW, ISI were decreased in contrast to the CON and HC groups (P < 0.05-0.01). In the Ir+ T2DM group, BW was higher, IRI, H/B, LVWI were lower than in the T2DM group. Compared with the CON and HC groups, the contents of col I and col III, the protein expressions of col I, AGE, RAGE, TIMP-2 and MMP-14 were increased, MMP-2 protein expression, the ratios of MMP-2/TIMP-2 and MMP-14/TIMP-2, MMP-2, and MMP-9 levels were decreased in the T2DM group (P < 0.01). After Irbesartan treatment, all parameters were reversed. Irbesartan can ameliorate myocardial fibrosis in type 2 diabetes rat model, the likely mechanisms may be related to the down-regulation of AGEs-RAGE system and changes of MMPs pathway.