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牛奶克菲尔疗法改善了接受糖皮质激素诱导骨质疏松症的大鼠对抗阻力运动的骨骼反应。

Milk kefir therapy improves the skeletal response to resistance exercise in rats submitted to glucocorticoid-induced osteoporosis.

机构信息

Post-Graduation Program in Morphofunctional Science, Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil; Nucleus of Study and Research in Pain, Inflammation and Osteoimmunology (NEPDIO), School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.

Nucleus of Study and Research in Pain, Inflammation and Osteoimmunology (NEPDIO), School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.

出版信息

Exp Gerontol. 2022 Oct 1;167:111921. doi: 10.1016/j.exger.2022.111921. Epub 2022 Aug 11.

Abstract

Glucocorticoid-induced osteoporosis (GIO) has emerged as a challenge after long-term glucocorticoids (GCs) administration. Exercise has been an important non-pharmacological option, while medications modulate bone remodeling despite adverse effects. In this way, milk Kefir (MK) therapy stands out as a safe alternative to improve bone metabolism. Our study aimed to investigate the effect of MK associated to resistance exercise on bone loss in rats with GIO. For this, sixty male Wistar rats were divided into 2 groups: normal (N) and subjected to GIO, which was subdivided into 4 groups: control (C), milk kefir therapy (K), Exercise (Ex), and Exercise+K (ExK). GIO was induced by dexamethasone (7 mg/kg - i.m.; 1×/wk, 5 wk). MK was administered daily (1×/day; 0.7 ml/animal) and the climb exercise with load was performed 3×/wk; both for 16 wk. Femur was collected for assessment of bone microarchitecture, quality and metabolism. GIO markedly reduced trabecular bone volume density (BV/TV) (-35 %), trabecular thickness (Tb.Th) (-33 %), mineral content of femur (-26 %) as well as bone collagen content (-56 %). Bone strength and its biomechanical properties given by flexural strength (-81 %), fracture load (-80 %), and the number of osteocytes (-84 %) were lowered after GIO. GCs reduced osteoblast number and function while increased osteoclast number, altering bone remodeling (p < 0.05). On the other hand, ExK significantly improved bone microarchitecture and quality, marked by fractal dimension increase (+38 %), cortical volume (+34 %), BV/TV (+34 %), Tb.Th (+33 %), mineral content and collagen maturity, while reduced the space between trabecula (-34 %). The Ex and ExK increased the number of osteocytes (p < 0.05) and they were able to reverse the lower osteoblast number. Both treatments used alone significantly enhanced bone biomechanical properties, but the ExK showed a more significant improvement. ExK ameliorated bone strength and biomechanics (p < 0.05) and stimulated bone formation and modulated bone remodeling (p < 0.05). MK and exercise administered isolated or in association increased the percentage of collagen bone filling after GIO (p < 0.05), but only ExK improved collagen maturity. Our results showed that MK associated to resistance exercise enhanced bone microarchitecture, quality and metabolism, being therefore an interesting tool to improve skeletal response during GIO.

摘要

糖皮质激素诱导的骨质疏松症(GIO)是长期使用糖皮质激素(GCs)后的一个挑战。运动是一种重要的非药物选择,而药物尽管有不良反应,但能调节骨重塑。在这方面,牛奶克菲尔(MK)疗法作为一种安全的替代方法,可改善骨代谢。我们的研究旨在探讨 MK 联合抗阻运动对 GIO 大鼠骨丢失的影响。为此,将 60 只雄性 Wistar 大鼠分为正常(N)和 GIO 两组,GIO 又分为对照组(C)、牛奶克菲尔治疗组(K)、运动组(Ex)和运动+牛奶克菲尔组(ExK)。用地塞米松(7mg/kg - i.m.;1×/wk,5 wk)诱导 GIO。MK 每日给药(1×/天;0.7ml/动物),并进行负重爬梯运动,每周 3 次;均进行 16 周。收集股骨评估骨微结构、质量和代谢。GIO 显著降低了骨小梁体积密度(BV/TV)(-35%)、骨小梁厚度(Tb.Th)(-33%)、股骨矿物质含量(-26%)和骨胶原含量(-56%)。骨强度及其生物力学性能(弯曲强度降低 81%、骨折负荷降低 80%、成骨细胞数量降低 84%)在 GIO 后也降低。GCs 减少了成骨细胞的数量和功能,而增加了破骨细胞的数量,改变了骨重塑(p<0.05)。另一方面,ExK 显著改善了骨微结构和质量,表现为分形维数增加(+38%)、皮质体积增加(+34%)、BV/TV 增加(+34%)、Tb.Th 增加(+33%)、矿物质含量和胶原成熟度增加,而小梁间空间减少(-34%)。Ex 和 ExK 增加了成骨细胞的数量(p<0.05),并能够逆转成骨细胞数量的减少。单独使用两种治疗方法均可显著提高骨生物力学性能,但 ExK 显示出更显著的改善。ExK 改善了骨强度和生物力学性能(p<0.05),刺激了骨形成并调节了骨重塑(p<0.05)。MK 和运动单独或联合使用均可增加 GIO 后胶原骨填充的百分比(p<0.05),但只有 ExK 改善了胶原成熟度。我们的结果表明,MK 联合抗阻运动增强了骨微结构、质量和代谢,因此是改善 GIO 期间骨骼反应的一种有趣工具。

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