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目的研究沙格列汀和艾塞那肽对糖尿病性骨质疏松大鼠肱骨松质骨的影响。方法 35只雌性SD大鼠随机分为正常组、对照组和待建模组,待建模组大鼠采用高脂高糖饮食喂养联合低剂量链脲佐菌素(30 mg·kg~(-1))诱导2型糖尿病,以注射链脲佐菌素10 d后口服葡萄糖耐量试验2 h大于11.1 mmol·L~(-1)、最高血糖大于16.7 mmol·L~(-1)为成模标准,筛选出糖尿病模型大鼠并随机分为模型组、沙格列汀组和艾塞那肽组,给药30 d后处死大鼠,分取左侧肱骨上段,4%多聚甲醛固定48 h,脱水透明后,采用甲基丙烯酸甲酯塑料包埋技术制作标本,切片后经Masson-Goldner Trichrome染色,以骨组织形态计量学分析骨量、骨结构变化情况。结果松质骨形态学结果:正常组、对照组无显著差异,与对照组相比,模型组大鼠松质骨的骨量显著丢失(P<0.01),骨小梁数目明显降低(P<0.01),分离度明显增加(P<0.01);与模型组相比,沙格列汀组、艾塞那肽组大鼠松质骨的骨量显著增加(P<0.01),骨小梁数目明显升高(P<0.01),分离度明显减小(P<0.01)。松质骨细胞参数:正常组、对照组无显著差别,与对照组相比,模型组大鼠的成骨细胞数(P<0.05)及成骨细胞周长百分数(P<0.01)明显降低,破骨细胞数及破骨细胞周长百分数显著上升(P<0.01);与模型组相比,沙格列汀组、艾塞那肽组大鼠的成骨细胞数(P<0.01)及成骨细胞周长百分数(沙格列汀组P<0.05,艾塞那肽组P<0.01)均显著上升,而两组的破骨细胞数(P<0.01)、破骨细胞周长百分数(P<0.05)均显著下降。肱骨生长板:正常组、对照组无显著差别,与对照组相比,模型组大鼠的生长板厚度明显降低(P<0.01)、肥大细胞直径显著减少(P<0.01);与模型组相比,沙格列汀组、艾塞那肽组大鼠的生长板厚度(P<0.01)和肥大细胞直径(P<0.05)均明显增加。结论沙格列汀和艾塞那肽均呈现对大鼠糖尿病性骨质疏松的治疗作用,其机制可能与二者改善生长板的生长率、改变糖尿病造成的低骨转换状态有关。
Objective To study the effect of saxagliptin and exenatide on humerus cancellous bone in diabetic rats. Methods Thirty - five female Sprague - Dawley rats were randomly divided into normal group, control group and model group. The rats in the model group were fed with high fat and high glucose diet and low - dose streptozotocin (30 mg · kg - 1)) induced type 2 diabetes mellitus. After oral streptozotocin injection for 10 days, the oral glucose tolerance test was more than 11.1 mmol·L -1 for 2 h and the maximum blood glucose was more than 16.7 mmol·L -1 The diabetic rats were selected and randomly divided into model group, saxagliptin group and exenatide group. Rats were sacrificed 30 days after the administration, and the left upper humerus was divided into four groups and fixed with 4% paraformaldehyde h, after dewatering and transparent, using methyl methacrylate plastic embedding technique to make specimens sliced by Masson-Goldner Trichrome stained with bone histomorphometry analysis of bone mass, bone structure changes. Results The cancellous bone morphological results showed that there was no significant difference between the normal group and the control group. Compared with the control group, the amount of cancellous bone in the model group was significantly lost (P <0.01) and the number of trabecular bone was significantly decreased (P < 0.01) and the degree of separation significantly increased (P <0.01). Compared with the model group, the amount of cancellous bone in the saxagliptin and exenatide groups increased significantly (P <0.01), the number of trabecular (P <0.01), and the resolution was significantly decreased (P <0.01). Compared with the control group, the number of osteoblast (P <0.05) and the percentage of osteoblast perimeter (P <0.01) in model group were significantly lower than those in control group The number of osteoclasts and the percentage of osteoclasts increased significantly (P <0.01). Compared with model group, the number of osteoblasts (P <0.01) and the percentage of osteoblast The percentages of osteocyte perimeter (P <0.05 in saxagliptin group and P <0.01 in exenatide group) were significantly higher than those in exenatide group (P <0.01). The percentage of osteoclast perimeter <0.05) decreased significantly. The humerus growth plate: There was no significant difference between normal group and control group. Compared with control group, the thickness of growth plate in model group was significantly decreased (P <0.01), and the diameter of mast cells was significantly reduced (P <0.01) The growth plate thickness (P <0.01) and mast cell diameter (P <0.05) were significantly increased in both saxagliptin and exenatide groups. Conclusions Both saxagliptin and exenatide show a therapeutic effect on diabetic osteoporosis in rats. The mechanism may be related to improving the growth rate of growth plate and changing the state of low bone turnover caused by diabetes.