二甲双胍对骨质疏松大鼠晚期糖基化终产物影响的研究

目的:探讨通过应用二甲双胍干预双侧卵巢摘除大鼠血清中晚期糖基化终产物变化从而调控骨代谢的可行性。方法:使用SD雌鼠通过行双侧卵巢摘除术或假手术建立停经后骨质疏松症模型(OVX组)及对照组模型(Sham组),3月后给予不同剂量二甲双胍灌胃,分为4组,分别是Sham组,OVX组,OVX+50 mg/kg/d二甲双胍组 ,OVX+100 mg/kg/d二甲双胍组,3月后处死大鼠,应用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)比较晚期糖基化终产物(AGEs)在血清中的表达差异。结果:与Sham组相比,OVX组大鼠的胫骨骨质明显呈现疏松多孔样,血清中AGEs含量明显升高;灌胃二甲双胍后,胫骨骨质量改善,骨小梁分布较OVX组密集,同时血清中AGEs含量较OVX组显著降低,但尚未达到Sham组水平,而OVX+50 mg/kg/d二甲双胍组与OVX+100 mg/kg/d二甲双胍组大鼠血清中AGEs含量无明显差异。结论: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。[关键词] 二甲双胍 绝经后骨质疏松症 晚期糖基化终产物

Effect of Metformin on Advanced Glycation End Products in Ovariectomized Rats.

Objective: To investigate the effect of metformin on serum advanced glycation end products (AGEs) in ovariectomized (OVX) rats. Methods: Forty female SD rats underwent bilateral ovariectomy or sham operation, three months later they were randomly assigned into four groups for metformin treatment: Sham rats, OVX rats, OVX+50 mg/kg/day rats, and OVX+100 mg/kg/day rats. Another three months later, all rats were sacrificed to evaluate the histology differences between different groups and to compare the serum AGEs differences by enzyme-linked immunosorbent assay (ELISA). Results: Compared with Sham group, bilateral ovariectomy induced impaired bone mass and increased serum AGEs; while metformin treatment significantly reversed these actions, leading to improved bone mass and decreased serum AGEs. However, there was no significant difference between OVX+50 mg/kg/day rats and OVX+100 mg/kg/day rats. Conclusion: Metformin may have a direct inhibition effect on bone loss in postmenopausal osteoporosis, and this action could be partly mediated through regulating AGEs levels in vivo.