Objectives The aim of this experiment was to study the significance of UII and its receptor UT, and endothelial- to- mesenchymal transition (EndMT) during development of myocardial fibrosis in a rat model of diabetic mellitus fed with fructose.
Methods Male SD rats (200 g), were randomly divided into 4 groups (n = 6-11): Control group; Metformin group [(treated with metformin (300 mg/kg·d) by gavage (8th-15th week)]; Fructose group (treated with 10% fructose in drinking water for 15 weeks); Fructose + Metformin group [treated with both fructose and metformin]. The changes of fasting blood-glucose and serum insulin, HDL, Masson staining, were observed. UII and TGF-β1 content were measured by radioimmunoassay. UT, α-SMA, fibroblast specific protein-1 (FSP-1) and collagen-I immunoreactivity in heart were detected by immunohistochemistry.
Results Fasting blood-glucose and insulin level in the fructose group were higher than that of control group and /or the metformin groups (both p < 0.05), while which in the fructose + metformin group were lower than the fructose group (both p < 0.01). HDL levels in the fructose group and the fructose + metformin group were lower than the controls (p < 0.01). In addition, myocardial fibrosis was significant in the fructose group, the collagen content of it was higher than the other three groups (p < 0.05), which was decreased significantly in the fructose + metformin group than the fructose group (p < 0.05). Moreover, the immunoreactivity of myocardial α-SMA, FSP-1 and collagen-I of fructose group was higher (p < 0.05) than that of the control and metformin group, which in the heart of fructose + metformin group was decreased (p < 0.05) than the fructose group. VE-cadherin from rats heart of fructose group was lower than that of the control and metformin group (p < 0.05), which in the metformin-fructose group was higher than that of fructose group (p < 0.05). Both cardiac and aortic TGF-β1 contents in the fructose rats was significantly higher than that in the control group (p < 0.05), while aortic TGF-β1 contents in fructose + metformin group was less than that of the fructose group (p < 0.01). Furthermore, the plasma UII content in fructose + metformin group was higher than that of metformin group (p < 0.05), but there was no significant difference between fructose and controls, and between the fructose and the fructose + metformin group. Myocardial and aortic UII contents in fructose group was higher (p < 0.001 in heart, and p < 0.05 in aorta) than the control and metformin group. The myocardial UII in the metformin + fructose group was lower than the fructose group. UT immunoreactivity in myocardium of fructose group was significantly increased than the control and metformin group, while it in the fructose + metformin group was lower than that of the fructose group.
Conclusions The results showed that both myocardial UII and UT expression are elevated, with the emergence of EndMT, during the development of cardiac fibrosis induced by diabetes mellitus in rats fed with fructose, indicating that UII may play an important role in diabetic myocardial fibrosis through EndMT.