GLP-1受体激动剂利拉鲁肽对糖皮质激素性骨质疏松大鼠的疗效和作用机制研究
Efficacy of GLP-1 receptor agonist liraglutide on bone metabolism and bone microstructure in glucocorticoid-induced osteoporosis in rats
  
DOI:10.3969/j.issn.1006-7108.2019.08.009
中文关键词:  利拉鲁肽  糖皮质激素性骨质疏松  Micro-CT  骨生物力学
英文关键词:liraglutide  glucocorticoid-induced osteoporosis  micro-CT  bone biomechanics
基金项目:安徽省高等学校自然科学研究重点项目(KJ2017A174)
作者单位
杨丽娜 杨靖 李娜 潘天荣 钟兴 安徽医科大学第二附属医院内分泌科安徽 合肥 230601 
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中文摘要:
      目的 讨论GLP-1受体激动剂利拉鲁肽对糖皮质激素性骨质疏松(GIOP)大鼠模型骨代谢指标的影响,包括对骨量、骨组织微结构、骨生物力学、骨转换标志物的作用。方法 选取30只8周龄雄性SD大鼠,随机分为对照组、地塞米松组、利拉鲁肽干预组,每组各10只。除对照组外,各组均予以地塞米松1 mg/kg肌肉注射(2次/周)诱导糖皮质激素性骨质疏松。利拉鲁肽组同时给予利拉鲁肽200 μg/(kg?d)皮下注射干预。对照组给予同等体积0.9%氯化钠肌肉注射。干预12周后收集两侧股骨和第五腰椎行Micro-CT和骨生物力学检测。同时收集外周血清检测抗酒石酸酸性磷酸酶(StrACP)、Ⅰ型胶原交联羧基端肽(CTX-1)、碱性磷酸酶(ALP)、和骨钙素(OC)。结果 地塞米松组股骨远端干骺端和第五腰椎的骨密度(BMD)、组织骨密度(TMD)、骨体积分数(BV/TV)、骨小梁分离度(Tb.Sp)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、连接密度(Conn.D)、最大载荷和弹性模量均较对照组明显降低,骨吸收指标TrACP、CTX-1显著升高,骨形成指标ALP、OC 显著降低(均P<0.05)。利拉鲁肽干预组大鼠的骨密度、骨微结构、骨生物力学指标得到明显改善,且TrACP、CTX-1明显降低,ALP、OC明显升高(均P<0.05)。结论 利拉鲁肽能对抗糖皮质激素的致骨质疏松作用,改善糖皮质激素造成的骨质疏松状态,机制可能与减少骨吸收以及促进骨形成有关。
英文摘要:
      Objective To investigate the effect of GLP-1 receptor agonist liraglutide on bone metabolism markers in rats with glucocorticoid-induced osteoporosis (GIOP), including the effects on bone mass, bone tissue microstructure, bone biomechanics, and bone turnover markers. Methods Thirty male 8-week-old Sprague–Dawley rats were randomly divided into 3 groups: control, model, and liraglutide intervention group. The rats in model and intervention groups were intramuscularly injected with dexamethasone at 1 mg/kg (twice a week) to induce GIOP. Simultaneously, the rats in intervention group was subcutaneously injected with liraglutide at 200 ?g/kg daily. The control group was intramuscularly injected with an equal volume of 0.9% sodium chloride. The bilateral femurs and the fifth lumbar vertebrae were collected in 12 weeks to perform micro-computed tomography and bone biomechanical examinations. Also, tartrate-resistant acid phosphatase (TrACP), cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I), alkaline phosphatase (ALP), and osteocalcin (OC) were tested. Results The bone mineral density (BMD) of the distal femurs and L5, TMD, BV/TV, Tb.Sp, Tb.Th, Tb.N, Conn.D, and bone biomechanical markers reduced significantly in the dexamethasone group compared with those in the control group. The bone resorption indicators TrACP and CTX-I increased, while the bone formation indicators ALP and OC decreased. After liraglutide treatment, BMD, bone microstructure, and bone biomechanical markers improved significantly. Moreover, TrACP and CTX-I decreased significantly, while ALP and OC increased compared with the model group. Conclusion Liraglutide antagonizes GIOP and relieves osteoporosis status. The protective mechanism might be related to a reduction in bone resorption and a promotion of bone formation.
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