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续断多糖通过调控 RANKL/RANK/OPG/VEGF 和 PI3K/Akt/eNOS 通路对体内骨质疏松的保护作用。

Protective effects of Dipsacus asper polysaccharide on osteoporosis in vivo by regulating RANKL/RANK/OPG/VEGF and PI3K/Akt/eNOS pathway.

机构信息

Department of Orthopaedic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China.

Department of Orthopaedic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China.

出版信息

Int J Biol Macromol. 2019 May 15;129:579-587. doi: 10.1016/j.ijbiomac.2019.02.022. Epub 2019 Feb 5.

Abstract

A homogenous polysaccharide (DAP), with a molecular weight of 2.61 × 10 Da, was isolated from the roots of Dipsacus asper Wall. Gas chromatography (GC) indicated that DAP was composed of galactose and mannose with a molar ratio of 1:1. The purpose of this study was to evaluate the effect of DAP on the progress of bone loss in the ovariectomized (OVX) rat model of osteoporosis. Administration of DAP (50 and 200 mg/kg/body wt. day) for 12 weeks significantly prevented OVX-induced bone loss, biomechanical reduction, the body weight gain, the loss of the uterus weight, as well as increased U-Ca/Cr, U-P/Cr, ALP, TRAP, OC and DPD/Cr levels in rats, which was further supported by the histopathological examinations. Furthermore, we found that the mechanism by which DAP elicited anti-osteoporotic effects was mediated by up-regulation of VEGF and OPG, but down-regulation of RANK and RANKL in both protein and mRNA expression in OVX rats, as well as the activation of PI3K/Akt/eNOS signaling pathway, indicating that DAP can be clinically used as a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis.

摘要

从川续断科植物续断(Dipsacus asper Wall)的根部分离得到一种均一的多糖(DAP),其分子量为 2.61×10 Da。气相色谱(GC)表明,DAP 由半乳糖和甘露糖组成,摩尔比为 1:1。本研究旨在评估 DAP 对去卵巢骨质疏松症大鼠模型骨丢失进展的影响。DAP(50 和 200mg/kg/体重/天)给药 12 周可显著预防 OVX 引起的骨丢失、生物力学降低、体重增加、子宫重量减轻,以及大鼠 U-Ca/Cr、U-P/Cr、ALP、TRAP、OC 和 DPD/Cr 水平升高,组织病理学检查进一步证实了这一点。此外,我们发现 DAP 发挥抗骨质疏松作用的机制是通过上调 VEGF 和 OPG,同时下调 OVX 大鼠蛋白和 mRNA 表达中的 RANK 和 RANKL,以及激活 PI3K/Akt/eNOS 信号通路来介导的,表明 DAP 可作为预防和治疗绝经后骨质疏松症的潜在替代药物在临床上使用。

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