二甲双胍骨保护效应中晚期糖基化终产物的作用机制

发布时间：2018-03-09 12:30

本文选题：二甲双胍　切入点：绝经后骨质疏松症　出处：《山西医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:探讨不同浓度二甲双胍对去势大鼠胫骨的骨密度(Bone mineral density,BMD)和骨生物力学的影响,探讨通过应用二甲双胍干预双侧卵巢摘除大鼠,检测血清中晚期糖基化终产物变化从而确定其调控骨代谢的可行性,从而为骨质疏松症的临床药物防治提供依据。方法:使用SD雌鼠通过行假手术或双侧卵巢摘除术建立对照组模型(Sham组)及停经后骨质疏松症模型(OVX组),分为4组,分别是Sham组,OVX组,OVX+50 mg/kg/day二甲双胍组,OVX+100 mg/kg/day二甲双胍组。3月后给予不同剂量二甲双胍灌胃,Sham组、OVX组给予相应剂量0.9%生理盐水,OVX+50mg/kg/day二甲双胍组、OVX+100 mg/kg/day二甲双胍组分别按50 mg/kg/day、100 mg/kg/day灌胃二甲双胍。3月后处死大鼠,取血清、胫骨标本,应用双能X线、生物力学、组织学方法检测不同组别大鼠骨质差异,应用酶联免疫吸附试验(ELISA)检测并比较各组大鼠血清中晚期糖基化终产物(AGEs)表达水平及差异。结果:与Sham组相比,OVX组大鼠的胫骨骨质呈现明显的疏松多孔样,骨密度明显降低(P0.05),弹性模量和最大载荷也显著下降(P0.05),血清中AGEs含量明显升高(P0.05),灌胃二甲双胍后,胫骨质量有所改善,骨小梁分布较OVX组密集,骨密度升高(P0.05),弹性模量和最大载荷也增加(P0.05),同时血清中AGEs含量较OVX组显著降低(P0.05),但均尚未达到Sham组水平(P0.05)。OVX+50 mg/kg/day二甲双胍组与OVX+100 mg/kg/day二甲双胍组实验结果比较发现:两组大鼠血清中AGEs含量接近(P0.05),骨质量、骨密度无明显差异(P0.05),但弹性模量和最大载荷表现出剂量相关性(P0.05)。结论:1、二甲双胍可提高去势大鼠骨密度及骨生物力学参数,具有改善停经后骨质疏松性骨折的作用。2、二甲双胍可能通过降低绝经后骨质疏松大鼠血清中的AGEs含量进而改善骨代谢。
[Abstract]:Objective: to investigate the effects of metformin at different concentrations on bone mineral density (BMD) and bone biomechanics in ovariectomized rats, and to explore the effect of metformin on bilateral ovariectomized rats. To determine the feasibility of regulating bone metabolism by detecting the changes of advanced glycation end products in serum. Methods: SD female rats were used to establish control group by sham-operation or bilateral ovariectomies) and postmenopausal osteoporosis model OVX group were divided into 4 groups. OVX 50 mg / kg / kg / day metformin group OVX 100 mg/kg/day metformin group respectively. After March, different doses of metformin were given intragastrically to the 0.9% normal saline group with 50 mg / kg mg/kg/day / kg metformin group, and the OVX 100 mg/kg/day metformin group were given OVX 100 mg/kg/day metformin group respectively, after March, the OVX group received 50 mg / kg of normal saline and 50 mg / kg 路kg / day metformin group respectively, and the OVX 100 mg/kg/day metformin group was given OVX100 mg/kg/day metformin group respectively after March. The rats were given metformin at 50 mg / kg / kg / 100 mg/kg/day. After March, the rats were killed. Serum and tibia samples were collected and bone difference of different groups of rats was detected by dual-energy X-ray, biomechanics and histology. Enzyme linked immunosorbent assay (Elisa) was used to detect and compare the expression of advanced glycation end products (ages) in the serum of rats in each group. Results: compared with Sham group, the tibial bone of rats in OVX group was obviously porous and porous. The bone mineral density (BMD) decreased significantly (P 0.05), the modulus of elasticity and the maximum load also decreased significantly (P 0.05). The content of AGEs in serum increased significantly (P 0.05). After intragastric administration of metformin, the tibia quality was improved, and the distribution of bone trabeculae was denser than that in the OVX group. The content of AGEs in serum was significantly lower than that in OVX group, but it was still not up to the level of Sham group. OVX 50 mg/kg/day metformin group and OVX 100 mg/kg/day metformin group were compared with OVX 100 mg/kg/day metformin group. The content of AGEs in serum of the two groups was close to that of P0. 05, and the bone mass of the two groups was higher than that of the control group. There was no significant difference in bone mineral density (BMD), but there was a dose-dependent correlation between the modulus of elasticity and the maximum load. Conclusion the bone mineral density and bone biomechanical parameters of ovariectomized rats can be increased by 1: 1 and metformin. Metformin may improve bone metabolism by reducing serum AGEs content in postmenopausal osteoporosis rats.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R580

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