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GW24-e0021 Bosentan ameliorates fibrotic agents in diabetic mice
  1. Yang Bo,
  2. Li Min,
  3. Yang Bo
  1. PLA General Hospital

Abstract

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.

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