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磷酸二酯酶-5 抑制剂可改善造影剂肾病大鼠模型的结构性肾损伤。

Phosphodiesterase-5 inhibitors ameliorate structural kidney damage in a rat model of contrast-induced nephropathy.

机构信息

Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania.

Department of Biochemistry, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania.

出版信息

Food Chem Toxicol. 2020 Sep;143:111535. doi: 10.1016/j.fct.2020.111535. Epub 2020 Jul 2.

Abstract

The aim of the study was to investigate the potential of sildenafil and tadalafil to ameliorate structural kidney damage in contrast-induced nephropathy (CIN). A rat model of CIN was developed by dehydration, administration of a nitric oxide inhibitor and a prostaglandin synthesis inhibitor (L-NAME/indomethacin) and contrast media exposure to iopromide. The effect of pre-treatment with sildenafil, tadalafil or N-acetyl cysteine (NAC) for 7 days prior to CIN induction was investigated. All animals were sacrificed at 24 h after CIN induction and both kidneys were collected. Histopathological examination was performed under light microscopy in serial tissue sections stained with hematoxylin and eosin. CIN group showed hydropic changes of the renal tubules (proximal and distal convoluted tubules and Henle's loop), an increased Bowman space with lobulated glomerulus and alteration of macula densa region of distal convolute tubules. The groups pretreated with sildenafil and tadalafil showed nearly normal histological aspects of renal tissue. The group pretreated with NAC showed similar but less intense histopathologic changes compared to CIN group. Sildenafil and tadalafil pre-treatment ameliorates CIN-related structural kidney damage and the protective potential of these agents is superior to NAC.

摘要

本研究旨在探讨西地那非和他达拉非改善对比剂肾病(CIN)结构肾损伤的潜力。通过脱水、给予一氧化氮抑制剂和前列腺素合成抑制剂(L-NAME/吲哚美辛)以及对比剂暴露于碘普罗胺,建立了 CIN 的大鼠模型。研究了在 CIN 诱导前 7 天用西地那非、他达拉非或 N-乙酰半胱氨酸(NAC)预处理对 CIN 诱导的影响。所有动物均在 CIN 诱导后 24 小时处死,采集双侧肾脏。用苏木精和伊红染色的连续组织切片在光镜下进行组织病理学检查。CIN 组表现为肾小管(近端和远端曲管和亨利氏环)水肿、肾小球分叶状的Bowman 空间增大和远端曲管的致密斑区域改变。用西地那非和他达拉非预处理的组显示出几乎正常的肾脏组织学特征。用 NAC 预处理的组与 CIN 组相比,表现出相似但较弱的组织病理学变化。西地那非和他达拉非预处理可改善 CIN 相关的结构肾损伤,这些药物的保护作用优于 NAC。

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