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阿朴酯素联合药物作为辅助治疗可用于预防和/或治疗慢性肾脏病。

Apocynin combined with drugs as coadjuvant could be employed to prevent and/or treat the chronic kidney disease.

机构信息

a Laboratorio de Investigación en Enfermedades Crónico Degenerativas, Sección de Estudios de Posgrado e Investigación, Departamento de Formación Básica Disciplinaria, Escuela Superior de Medicina , Instituto Politécnico Nacional , Ciudad de México , México.

b Sección de Estudios de Posgrado e Investigación, Departamento de Formación Básica Disciplinaria, Escuela Superior de Medicina , Instituto Politécnico Nacional , Ciudad de México , México.

出版信息

Ren Fail. 2018 Nov;40(1):92-98. doi: 10.1080/0886022X.2017.1421557.

Abstract

A worldwide public health problem is chronic kidney disease (CKD) presenting alarming epidemiological data. It currently affects about 10% of the adult population worldwide and has a high mortality rate. It is now known that oxidative stress represents one of the most important mechanisms in its pathophysiology, from the early stages to the terminal phase. Oxidation increases inflammation and reduces the capacity of NO to relax vascular smooth muscle, in part by decreasing bioavailability of tetrahydrobiopterin (BH), leading to endothelial dysfunction and high blood pressure, and due to the limited effectiveness of existing treatments, new drugs are needed to prevent and/or treat these mechanisms. The aim of this study was to test apocynin in a 5/6 nephrectomy mouse model of CKD to investigate whether its known antioxidant effect can improve the disease outcome. This effect results from the inhibition of NADPH oxidase and consequently a reduced production of the superoxide anion ([Formula: see text]). Animals were divided into five groups: sham, 5/6 nephrectomy only, and 5/6 nephrectomy followed by treatment with captopril, losartan or apocynin. The parameters evaluated were blood pressure and markers of oxidative stress ([Formula: see text]) and endothelial function (BH4). There were significantly lower levels of [Formula: see text] and a greater availability of serum BH4 in the apocynin-treated animals versus the control group and the two other drug treatments. The present findings suggest that apocynin in conjunction with a coadjuvant for modulating blood pressure may be useful for controlling the progression of CRF.

摘要

一个全球性的公共卫生问题是慢性肾脏病(CKD),其呈现出令人震惊的流行病学数据。目前,它影响着全球约 10%的成年人,死亡率很高。现在已知氧化应激是其病理生理学中最重要的机制之一,从早期阶段到终末期都是如此。氧化应激增加炎症反应,降低一氧化氮松弛血管平滑肌的能力,部分原因是四氢生物蝶呤(BH)的生物利用度降低,导致内皮功能障碍和高血压,由于现有治疗方法的效果有限,需要新的药物来预防和/或治疗这些机制。本研究旨在在 5/6 肾切除的 CKD 小鼠模型中测试 apocynin,以研究其已知的抗氧化作用是否能改善疾病的结局。这种作用是通过抑制 NADPH 氧化酶,从而减少超氧阴离子 ([Formula: see text]) 的产生。动物被分为五组:假手术组、5/6 肾切除组、5/6 肾切除后用卡托普利、氯沙坦或 apocynin 治疗组。评估的参数包括血压和氧化应激标志物 ([Formula: see text]) 和内皮功能 (BH4)。与对照组和另外两种药物治疗组相比,apocynin 治疗组的 [Formula: see text] 水平显著降低,血清 BH4 的可用性增加。本研究结果表明,apocynin 与调节血压的辅助药物联合使用,可能有助于控制 CRF 的进展。

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