3-氧吡啶衍生物对大鼠类固醇性骨质疏松症的保护作用,与氧化应激减少和一氧化氮形成恢复有关

A. P. Danilenko, K. S. Trunov, M. Pokrovsky, L. M. Danilenko, M. V. Korokin, O. Gudyrev, A. Khentov, N. P. Masalytina, I. A. Tatarenkova, A. V. Cherednichenko, E. V. Boeva, I. S. Koklin, E. I. Taran
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摘要

从本文考虑的类固醇诱导骨质疏松症发病机制的角度来看,成骨细胞氧化应激风险的增加,以及骨组织微循环血流血管内皮功能障碍的发展,特别令人感兴趣。它们导致骨组织营养受损和骨质疏松症的发展。研究3-羟基吡啶衍生物对类固醇性骨质疏松模型的骨保护作用。材料和方法。以雄性Wistar大鼠为模型,每5天腹腔注射5 mg/kg剂量的甲基强的松龙(MP),连续5周。Аs是NO合成酶的非选择性阻断剂,L-NAME的剂量为25 mg/kg(腹腔)。3-羟基吡啶衍生物(以下简称1号制剂)以50 mg/kg(每os)的剂量给药,对各实验组小鼠微循环水平、骨密度进行测定,并对组织形态学和生化样品进行分析。研究结果表明,组合物1 (50 mg/kg)具有骨保护活性,有效防止局部骨组织微循环水平下降和内皮功能障碍的发生。这使得增加骨密度和减缓骨小梁变薄成为可能。此外,组合物1 (50 mg/kg)可减少活性氧的产生,提高No的生物利用度。所获得的数据表明,所研究的3-羟基吡啶衍生物被认为是预防和治疗类固醇性骨质疏松症的有前途的化合物。
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Protective role of 3-oxypyridine derivatives in rats’ steroid-induced osteoporosis associated with reduced oxidative stress and recovery of nitric oxide formation
From the point of view of the mechanisms for the implementation of pathogenetic links in the development of steroid-induced osteoporosis considered in the paper, the increased risk of the oxidative stress in osteoblasts, as well as the development of the vessels endothelial dysfunction of the microcirculatory bloodstream in the bone tissue, are of particular interest. They lead to the impaired bone tissue trophism and progression of osteoporosis.The aim of the study was research of the osteoprotective effects of a 3-hydroxypyridine derivatives composition on the model of steroid-induced osteoporosis.Materials and methods. To model osteoporosis pathology, the animals (male Wistar rats) were injected with methylprednisolone (MP) at the dose of 5 mg/kg (intraperitoneally) every 5th day for 5 weeks. Аs a non-selective blocker of NO synthase, L-NAME was used at the dose of 25 mg/kg (intraperitoneally). Derivatives of 3-hydroxypyridine (hereinafter referred to as composition No. 1) were administrated at the dose of 50 mg/kg (per os) In all experimental groups, the level of microcirculation and the bone mineral density, as well as the analysis of histomorphological and biochemical samples, were assessed.Results. The study results showed that composition No. 1 (50 mg/kg) has an osteoprotective activity, effectively prevents a decrease in the level of the regional bone tissue microcirculation and in the development of an endothelial dysfunction. That makes it possible to increase the bone mineral density and to slow down the thinning of bone trabeculae. In addition, composition No. 1 (50 mg/kg) reduces the production of reactive oxygen species and increases the NO bioavailability.Conclusion. The data obtained indicate that the studied composition of 3-hydroxypyridine derivatives is considered a promising compound for the prevention and treatment of steroid-induced osteoporosis.
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