Objectives To investigate the potential beneficial effect of Bosentan in ameliorating fibrotic agents in diabetic mice.
Methods Male C57BL/6 mice with 6-week old were divided into 3 groups (N = 20) : Control group, DM group (diabetes group) and DM-B group (diabetes with Bosentan group). STZ was injected as 200 mg/Kg for single dose, i.p. (intraperitoneal injection). Fasting blood glucose (FBG) was measured at 0-, 1-, 2-week after STZ injection to confirm that diabetic model was made. Bosentan (100 mg/Kg) and placebo was given i.g. (intragastric administration) once a day immediately after STZ injection for 18 weeks. The mRNA expression of TGF-ß, CTGF, VEGF and Collagen-1 were evaluated by RT-PCR and real-time PCR.
Results After 18 weeks of diabetic situation, FBG of DM-B mice was significantly higher than that of Control mice and was similar with that of DM mice (DM mice vs. control mice, P < 0.001; DM-B vs. control mice, P < 0.001; DM mice vs. DM-B mice, P > 0.05). The cardiac VEGF mRNA (a potent angiogenic factor) level in DM-B mice was significantly higher than DM mice (P < 0.01). The heart of DM-B mice also showed lower expression of fibrotic genes (TGF-ß, CTGF and Collagen-1) than DM mice (P < 0.01).
Conclusions These findings indicate the potential usefulness of an ET receptor antagonist Bosentan in the amelioration of fibrotic agents, which may promote tissue fibrosis. This may provide a promising therapeutical strategy for diabetic cardiac fibrosis.