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血管紧张素转换酶2激活剂地泽对肾血管性高血压的有益作用。

Beneficial Effects of the Angiotensin-Converting Enzyme 2 Activator Dize in Renovascular Hypertension.

作者信息

Kangussu Lucas Miranda, de Almeida Tatiane Cristine S, Prestes Thiago Ruiz R, de Andrade De Maria Marilda Luz, da Silva Filha Roberta, Vieira Maria Aparecida Ribeiro, Silva Ana Cristina Simões E, Ferreira Anderson José

机构信息

Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.

Department of Pediatrics, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.

出版信息

Protein Pept Lett. 2019;26(7):523-531. doi: 10.2174/0929866526666190405123422.

Abstract

BACKGROUND

Angiotensin Converting Enzyme (ACE) 2 is an important modulator of the Renin Angiotensin System (RAS) and the RAS plays a central role in renovascular hypertension. Very few studies investigated the role of components of the counterregulatory RAS axis (ACE2, Ang-(1-7) and Mas receptor) in renovascular hypertension and the results are controversial.

OBJECTIVE

The aim of this study was to investigate the effects of Diminazene Aceturate (DIZE) administration on renal function and renal inflammation parameters in 2K1C hypertensive rats.

METHODS

Male Wistar rats were divided into three experimental groups: sham-operated animals, 2K1C+saline and 2K1C+DIZE orally (1 mg/kg/day). At the end of the 30 days of treatment, renal function was analyzed and kidneys from all the groups were collected and processed separately for measurement of N-acetyl-beta-D-glucosaminidase (NAG) and Myeloperoxidase (MPO) activities, cytokines, chemokines and nitric oxide levels.

RESULTS

Oral DIZE administration for 4 weeks in hypertensive rats attenuated renal dysfunction and reduced the levels of MPO and NAG, cytokines and chemokines (IL1β, IL-6, TNF-α and MCP-1) and increased urinary nitrate/nitrite levels in 2K1C hypertensive rats.

CONCLUSION

Our findings showed that ACE2 activation may effectively improve renal alterations and inflammation induced by renovascular hypertension.

摘要

背景

血管紧张素转换酶(ACE)2是肾素血管紧张素系统(RAS)的重要调节因子,而RAS在肾血管性高血压中起核心作用。很少有研究调查反调节RAS轴(ACE2、血管紧张素-(1-7)和Mas受体)的成分在肾血管性高血压中的作用,且结果存在争议。

目的

本研究旨在探讨乙酰氨基阿维菌素(DIZE)给药对2K1C高血压大鼠肾功能和肾炎症参数的影响。

方法

将雄性Wistar大鼠分为三个实验组:假手术动物组、2K1C+生理盐水组和2K1C+DIZE口服组(1mg/kg/天)。在治疗30天结束时,分析肾功能,并分别收集所有组的肾脏,用于测量N-乙酰-β-D-氨基葡萄糖苷酶(NAG)和髓过氧化物酶(MPO)活性、细胞因子、趋化因子和一氧化氮水平。

结果

高血压大鼠口服DIZE 4周可减轻肾功能障碍,降低MPO和NAG水平、细胞因子和趋化因子(IL1β、IL-6、TNF-α和MCP-1)水平,并增加2K1C高血压大鼠尿硝酸盐/亚硝酸盐水平。

结论

我们的研究结果表明,ACE2激活可能有效改善肾血管性高血压引起的肾脏改变和炎症。

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