Protective effect of bosentan on diabetic vascular disease in rats

Objective To investigate the potential beneficial effects of endothelin receptor antagonist bosentan on vascular disease in diabetic mice and its mechanism. Methods Sixty 6-week-old male C57BL/6 mice were divided into 3 groups:control group, diabetes group and diabetes with drug intervention group.Streptozotocin(STZ) was intraperitoneally injected at a single dose of 70 mg/kg to establish diabetes model.The fasting blood glucose from tail vein sample was tested to verify diabetes model.Bosentan(100 mg/kg) was given by intragastric administration once a day after STZ injection for 8 weeks in diabetes with drug intervention group, and the same amount of 0.9% sodium chloride injection was given to control group and diabetes group.After 8 weeks, aortic HE staining results in each group and mRNA expression of vascular endothelial growth factor(VEGF), endothelin-1(ET-1), tumor necrosis factorα(TNF-α), matrix metalloproteinases 2(MMP-2), matrix metalloproteinases 9(MMP-9) were observed by qRTPCR. Results HE staining results showed that aortic intima was generally normal in control group, while there were atherosclerotic plaque formation and a large number of inflammatory cell in diabetes group and the plaque burden lightened obviously in diabetes with drug intervention group.qRT-PCR results showed that the mRNA level of VEGF in diabetes group and diabetes with drug intervention group were significantly lower than those in control group(P< 0.05), while the mRNA expression of ET-1, TNF-a, MMP-2, MMP-9 in diabetic group and diabetes with drug intervention group increased significantly when compared with control group(P< 0.05).The mRNA expression of VEGF in diabetes with drug intervention group was higher than that in diabetes group(P< 0.05) and the mRNA expressions of ET-1, TNF-a, MMP-2 and MMP-9 in diabetes with drug intervention group were lower than those in diabetic group(P< 0.05). Conclusion Endothelin receptor antagonist bosentan has beneficial effects on vascular complications in diabetic mice.