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N-酰基葡糖胺类药物治疗骨与关节疾病:N-丁酰基葡糖胺对去卵巢大鼠骨骼的影响。

N-acylated glucosamines for bone and joint disorders: effects of N-butyryl glucosamine on ovariectomized rat bone.

机构信息

Division of Rheumatology and The Arthritis Center, Department of Medicine, Queen's University, Kingston, Ontario, Canada.

出版信息

Transl Res. 2013 Aug;162(2):93-101. doi: 10.1016/j.trsl.2013.04.002. Epub 2013 May 13.

Abstract

The benefit of glucosamine (GlcN) in bone and joint disorders remains controversial. N-acetylation and other N-acylations of GlcN alter its biological properties fundamentally. We have shown previously that N-butyryl glucosamine (GlcNBu) preserved strikingly the subchondral bone structure in a destructive arthritis rat model. Here, we examine whether GlcNBu preserves bone in the ovariectomized (OVX) rat, a model for postmenopausal osteoporosis. Rats were randomized into 4 groups: group 1, sham OVX glucose (Glc) fed; group 2, sham OVX GlcNBu fed; group 3, OVX Glc fed; and group 4, OVX GlcNBu fed. A single, oral, 200-mg/kg dose of GlcNBu or Glc was administered daily for 6 months. Bone mineral content (BMC) and bone mineral density, and biomechanical properties of the femurs and spines were determined by standardized techniques. Two-way analysis of variance with a Bonferroni post hoc test was used for statistical analysis. Ovariectomy in group 3 resulted either in significant or highly significant effects in a number of the tests. For spinal BMCs the interaction between GlcNBu and OVX was significant. For the femurs, this interaction was also seen in energy to failure, and ultimate displacement and ultimate strain tests. In general, ovariectomy was necessary to show significant preventive effects of GlcNBu on mineral content and some biomechanical properties. We conclude that GlcNBu feeding in the OVX rat preserves bone mineral and some biomechanical properties. Translationally, GlcNBu can be positioned between nutriceuticals and pharmaceuticals for the prevention and treatment of osteoporosis. Advantages include low production costs and a favorable safety profile.

摘要

氨基葡萄糖(GlcN)在骨骼和关节疾病中的益处仍存在争议。GlcN 的 N-乙酰化和其他 N-酰化从根本上改变了其生物学特性。我们之前已经表明,N-丁酰基氨基葡萄糖(GlcNBu)在破坏性关节炎大鼠模型中显著保留了软骨下骨结构。在这里,我们研究了 GlcNBu 是否能在去卵巢(OVX)大鼠中保留骨骼,去卵巢大鼠是绝经后骨质疏松症的模型。大鼠被随机分为 4 组:第 1 组,假去卵巢葡萄糖(Glc)喂养;第 2 组,假去卵巢 GlcNBu 喂养;第 3 组,OVX Glc 喂养;第 4 组,OVX GlcNBu 喂养。每天口服一次 200mg/kg 的 GlcNBu 或 Glc,持续 6 个月。通过标准化技术测定股骨和脊柱的骨矿物质含量(BMC)和骨矿物质密度以及生物力学特性。采用双向方差分析和 Bonferroni 事后检验进行统计学分析。第 3 组的卵巢切除术导致许多测试中出现显著或高度显著的影响。对于脊柱 BMC,GlcNBu 和 OVX 之间的相互作用是显著的。对于股骨,在失效能量、最大位移和最大应变测试中也观察到这种相互作用。一般来说,卵巢切除术是必要的,以显示 GlcNBu 对矿物质含量和一些生物力学特性的显著预防作用。我们的结论是,GlcNBu 喂养在 OVX 大鼠中可以保留骨矿物质和一些生物力学特性。从转化的角度来看,GlcNBu 可以定位于营养保健品和药物之间,用于预防和治疗骨质疏松症。其优点包括生产成本低和安全性良好。

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