1型糖尿病模型大鼠股骨骨代谢紊乱及唑来膦酸的影响

Effects of zoledronic acid on bone metabolism disturbance in the femur of type 1 diabetic rat models

背景:糖尿病引起的骨质疏松作为常见的继发性骨质疏松,近年来越来越受到重视;唑来膦酸作为新型治疗骨质疏松的药物,其对体内成骨细胞的作用尚未完全清楚。目的:观察1型糖尿病大鼠股骨干骺端骨形态发生蛋白2与Noggin的表达变化,以及唑来膦酸的干预作用。方法:随机取130只Wistar大鼠腹腔注射链脲佐菌素建立1型糖尿病模型,3 d后连续3次血糖>16.7 mmol/L鼠为造模成功鼠,共120只,随机等分为模型组、预防组和治疗组。后2组大鼠分别在造模后当天和2周后一次性静脉给予唑来膦酸(0.1 mg/kg)。另取40只大鼠注射柠檬酸缓冲液作为对照组。结果与结论:与对照组相比,模型组大鼠股骨骨密度、血清碱性磷酸酶水平、股骨骨形态发生蛋白2 mRNA表达水平明显降低(P<0.05),Noggin mRNA表达水平显著升高(P<0.05)。与模型组相比,预防组和治疗组大鼠骨密度和骨形态发生蛋白2 mRNA表达水平显著升高(P<0.05),Noggin mRNA表达水平显著降低(P<0.05),血清骨碱性磷酸酶水平也逐渐恢复。提示1型糖尿病大鼠骨代谢紊乱在病程早期即出现,而应用唑来膦酸可以促进骨形成,增加骨密度,改善骨代谢。

BACKGROUND： Osteoporosis caused by diabetes mellitus as common secondary osteoporosis has been paid more and more attention recently. Zoledronic acid serves as a novel drug for osteoporosis, and its effect on osteoblasts in vivo remains unclear. OBJECTIVE： To investigate the changes of the expression of bone morphogenetic protein 2 and Noggin in the femur of type 1 diabetes mellitus rats and the effect of zoledronic acid on them. METHODS： Models of type 1 diabetes mellitus were established by intraperitoneal injection of streptozotocin in 130 Wistar rats. 3 days later, rats with blood sugar 16.7 mmol/L for three consecutive times were considered as successful models, 120 in total. These models were randomly divided into model, prevention and treatment groups. Rats in the prevention and treatment groups were intravenously administered zoledronic acid（0.1 mg/kg） on the day of modeling and 2 weeks after model establishment. An additional 40 rats were injected with citrate buffer solution as control group. RESULTS AND CONCLUSION： Compared with the control group, femur bone mineral density, serum alkaline phosphatase levels, and femur bone morphogenetic protein 2 mRNA expression levels were significantly lower in the model group（P〈0.05）, but Noggin mRNA expression significantly increased（P〈0.05）. Compared with the model group, bone mineral density and bone morphogenetic protein 2 mRNA expression levels were significantly higher in the prevention and treatment groups（P〈0.05）, but Noggin mRNA expression significantly lower（P〈0.05）, and serum alkaline phosphatase levels gradually restored. These results indicated that the bone metabolic disturbance occurs in early stage in rats with type 1 diabetes mellitus. Zoledronic acid can promote bone formation, increase bone density, and improve bone metabolism.