Effects of saxagliptin and exenatide on humerus cancellous bone of diabetes-induced osteopenia rats / 中国药学杂志

ABSTRACT

OBJECTIVE: To determine the effects of saxagliptin and exenatide on humerus cancellous bone of diabetes-induced osteopenia rats by histomorphometry. METHODS: Thirty-five Cases of female SD rats were randomly divided into normal group (N group, n=7), control group (C group, n=7), and the remaining rats were used to establish the type 2 diabetic model by combination of high-fat&sugar-diet feeding for 4 weeks and then low-dose streptozotocin injection(STZ, 30 mg·kg-1). After 10 d, the oral glucose tolerance test and the fasting blood glucose were measured, rats with high OGTT(2 h) above 11.1 mmol·L-1 and high FBG above 16.7 mmol·L-1 were divided into model group (M group, n=5), saxagliptin group (G group, n=5) and exenatide group (D group,n=6), and continuously treated for 30 d. The left humerus (proximal humeru metaphometry, PHM) were fixed with 4% paraformaldehyde for 48 h, uncalcified embedded in methyl methacrylate after dehydrated and cleared, and sections were taken for bone histomorphometry after Masson-Goldner Trichrome stained. RESULTS: In PHM, there was no statistical significance between N and C group, the trabecular bone area ratio(BV/TV) and trabecular quantity were significantly decreased (P<0.01) in M group, while the trabecular separation degree was increased, comparing with those in C group (P<0.01), and the trabecular bone area ratio(BV/TV) and trabecular quantity in G and D group were higher (P<0.01) than those of model rats, while the trabecular separation degree was decreased, comparing with those in M group (P<0.01). Cell parameters showed no statistical significance between N and C group, the osteocllast number and percentage of osteocllast surface perimeter were significantly reduced(P<0.05, P<0.01) in M group, while the osteoclast number and percent osteocllast surface perimeter were significantly increased (P<0.01) as compared with those in C group, saxagliptin and exenatide were found to significantly induce osteocllast number (P<0.01) and percentage of osteoblast surface perimeter (G group P<0.05, D group P<0.01), while reduce osteoclast number (P<0.01) and percent osteoblast surface perimeter (P<0.05) compared with M group. In growth-plate, there was no statistical significance between N and C group, the thickness of growth-plate and the diameter of the mast cells were reduced in M groups (P<0.01), while the thickness of growth-plate (P<0.01) and the diameter of the mast cells (P<0.05) were increased in G and D group,compared with M group. CONCLUSION: Therapeutic effects of saxagliptin and exenatide on diabetes-induced osteopenia rats was showed, and the mechanism may be related to the improved growth rate of growth-plate and the changed bone turnover status.