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金纳米粒子慢性治疗对 Mdx 小鼠炎症反应和氧化应激的影响。

Effects of chronic treatment with gold nanoparticles on inflammatory responses and oxidative stress in Mdx mice.

机构信息

Laboratory of Experimental Phisiopatology, Universidade do Extremo Sul Catarinense, Criciúma, Brazil.

Laboratory of Exercise Biochemistry in Health, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

出版信息

J Drug Target. 2020 Jan;28(1):46-54. doi: 10.1080/1061186X.2019.1613408. Epub 2019 Jun 27.

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked recessive hereditary myopathy characterised by progressive muscle degeneration in male children. As a consequence of DMD, increased inflammation and oxidative stress occur in muscle tissue along with morphological changes. Several studies have reported anti-inflammatory and antioxidant effects of gold nanoparticles (GNP) in muscle injury models. The objective of this study was to evaluate these effects along with the impacts of the disease on histopathological changes following chronic administration of GNP to Mdx mice. Two-month-old Mdx mice were separated into five groups of eight individuals each, as follows: wild-type (WT), Mdx-modified without treatment, Mdx + 2.5 mg/kg GNP, Mdx + 7.0 mg/kg GNP and Mdx + 21 mg/kg GNP. GNP with a mean diameter of 20 nm were injected subcutaneously at concentrations of 2.5, 7.0 and 21 mg/kg. Treatments continued for 30 d with injections administered at 48-h intervals. Twenty-four hours after the last injection, the animals were killed and the central region of the gastrocnemius muscle was surgically removed. Chronic administration of GNP reduced inflammation in the gastrocnemius muscle of Mdx mice and reduced morphological alterations due to inflammatory responses to muscular dystrophy. In addition, GNP also demonstrated antioxidant potential by reducing the production of reactive oxygen and nitrogen species, reducing oxidative damage and improving antioxidant activity.

摘要

杜氏肌营养不良症(DMD)是一种 X 连锁隐性遗传性肌病,其特征是男性儿童的肌肉进行性退化。由于 DMD,肌肉组织中会发生炎症和氧化应激增加以及形态变化。几项研究报道了金纳米粒子(GNP)在肌肉损伤模型中的抗炎和抗氧化作用。本研究的目的是评估这些作用,以及疾病对慢性给予 GNP 的 Mdx 小鼠组织病理学变化的影响。将 2 个月大的 Mdx 小鼠分为五组,每组 8 只,如下所示:野生型(WT)、未经治疗的 Mdx 修饰型、Mdx+2.5mg/kg GNP、Mdx+7.0mg/kg GNP 和 Mdx+21mg/kg GNP。平均直径为 20nm 的 GNP 以 2.5、7.0 和 21mg/kg 的浓度皮下注射。以 48 小时的间隔进行 30 天的治疗,每次注射。最后一次注射后 24 小时,处死动物并从腓肠肌的中心区域进行手术切除。慢性给予 GNP 可减轻 Mdx 小鼠腓肠肌的炎症,并减轻由于肌肉营养不良引起的炎症反应导致的形态改变。此外,GNP 还通过减少活性氧和氮物种的产生、减少氧化损伤和提高抗氧化活性来显示出抗氧化潜力。

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