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阿拉曼丁可减轻小鼠横主动脉缩窄后右侧颈动脉的氧化应激。

Alamandine attenuates oxidative stress in the right carotid following transverse aortic constriction in mice.

机构信息

Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; National Institute of Science and Technology in Nanobiopharmaceutics (INCT-Nanobiofar), Belo Horizonte, Minas Gerais, Brazil.

Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Cancer & Cardiovascular Research Building, University of Minnesota, Minneapolis, MN, USA.

出版信息

Peptides. 2024 Jan;171:171094. doi: 10.1016/j.peptides.2023.171094. Epub 2023 Sep 9.

Abstract

OBJECTIVE

Pressure overload can result in significant changes to the structure of blood vessels, a process known as vascular remodeling. High levels of tension can cause vascular inflammation, fibrosis, and structural alterations to the vascular wall. Prior research from our team has demonstrated that the oral administration of alamandine can promote vasculoprotective effects in mice aorta that have undergone transverse aortic constriction (TAC). Furthermore, changes in local hemodynamics can affect the right and left carotid arteries differently after TAC. Thus, in this study, we aimed to assess the effects of alamandine treatment on right carotid remodeling and the expression of oxidative stress-related substances induced by TAC.

METHODS AND RESULTS

Male C57BL/6 mice were categorized into three groups: Sham, TAC, and TAC treated with alamandine (TAC+ALA). Alamandine treatment was administered orally by gavage (30 µg/kg/day), starting three days before the surgery, and continuing for a period of fourteen days. Morphometric analysis of hematoxylin and eosin-stained sections revealed that TAC induced hypertrophic and positive remodeling in the right carotid artery. Picrosirius Red staining also demonstrated an increase in total collagen deposition in the right carotid artery due to TAC-induced vascular changes. Alamandine treatment effectively prevented the increase in reactive oxygen species production and depletion of nitric oxide levels, which were induced by TAC. Finally, alamandine treatment was also shown to prevent the increased expression of nuclear factor erythroid 2-related factor 2 and 3-nitrotyrosine that were induced by TAC.

CONCLUSION

Our results suggest that alamandine can effectively attenuate pathophysiological stress in the right carotid artery of animals subjected to TAC.

摘要

目的

压力超负荷会导致血管结构发生显著变化,这一过程被称为血管重构。张力过高可引起血管炎症、纤维化和血管壁结构改变。我们团队的先前研究表明,口服 Alamandine 可促进经历过横主动脉缩窄(TAC)的小鼠主动脉的血管保护作用。此外,TAC 后局部血液动力学的变化会对右颈动脉和左颈动脉产生不同的影响。因此,在本研究中,我们旨在评估 Alamandine 治疗对右颈动脉重构以及 TAC 诱导的氧化应激相关物质表达的影响。

方法和结果

雄性 C57BL/6 小鼠分为三组:假手术组(Sham)、TAC 组和 TAC 加 Alamandine 治疗组(TAC+ALA)。Alamandine 通过灌胃(30μg/kg/天)进行口服给药,在手术前三天开始给药,并持续给药 14 天。苏木精和伊红染色切片的形态计量学分析显示,TAC 诱导右颈动脉发生肥大和正性重构。苦味酸天狼星红染色也表明,由于 TAC 引起的血管变化,右颈动脉总胶原沉积增加。Alamandine 治疗可有效防止 TAC 诱导的活性氧产生增加和一氧化氮水平降低。最后,Alamandine 治疗还可防止 TAC 诱导的核因子红细胞 2 相关因子 2 和 3-硝基酪氨酸表达增加。

结论

我们的研究结果表明,Alamandine 可有效减轻 TAC 动物右颈动脉的病理生理应激。

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