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伐地那非和阿伐那非在对比剂肾病中的肾脏保护作用:来自动物模型的新证据

Renoprotective Effect of Vardenafil and Avanafil in Contrast-Induced Nephropathy: Emerging Evidence from an Animal Model.

作者信息

Zisis Ioannis-Erineos, Georgiadis Georgios, Docea Anca Oana, Calina Daniela, Cercelaru Liliana, Tsiaoussis John, Lazopoulos Georgios, Sofikitis Nikolaos, Tsatsakis Aristidis, Mamoulakis Charalampos

机构信息

Department of Urology, University General Hospital of Heraklion, Medical School, University of Crete, 71003 Heraklion, Crete, Greece.

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

出版信息

J Pers Med. 2022 Apr 22;12(5):670. doi: 10.3390/jpm12050670.

Abstract

The potential renoprotective effects of vardenafil (VAR) have been evaluated in a very limited number of studies using acute kidney injury animal models other than contrast-induced nephropathy (CIN) with promising results, while avanafil (AVA) has not been evaluated in this respect before. The purpose of this study was to evaluate for the first time the potential renoprotective effect of VAR and AVA in a rat model of CIN. Twenty-five male Wistar rats were equally assigned into five groups: control, CIN, CIN+N-acetyl cysteine (NAC) (100 mg/kg/day) as a positive control, CIN+VAR (10 mg/kg/day) and CIN+AVA (50 mg/kg/day). CIN was induced by dehydration, inhibition of prostaglandin and nitric oxide synthesis as well as exposure to the contrast medium (CM). Serum Cr (sCr) levels were measured at 24 and 48 h after CIN induction. At 48 h of CM exposure, animals were sacrificed. Matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9, kidney injury molecule 1 (KIM-1) and cystatin-C (Cys-C) were measured on renal tissue. Histopathological findings were evaluated on kidney tissue. All treatment groups had close to normal kidney appearance. sCr levels subsided in all treatment groups compared to CIN group at 48 h following CIN induction. A significant decline in the levels of MMP-2, MMP-9, KIM-1 and Cys-C compared to CIN group was observed. These results provide emerging evidence that VAR and AVA may have the potential to prevent CIN.

摘要

在除造影剂肾病(CIN)之外的急性肾损伤动物模型中,仅有非常有限的研究评估了伐地那非(VAR)的潜在肾脏保护作用,结果令人鼓舞,而阿伐那非(AVA)此前尚未在这方面进行评估。本研究的目的是首次在CIN大鼠模型中评估VAR和AVA的潜在肾脏保护作用。将25只雄性Wistar大鼠平均分为五组:对照组、CIN组、CIN + N - 乙酰半胱氨酸(NAC)(100 mg/kg/天)作为阳性对照组、CIN + VAR(10 mg/kg/天)组和CIN + AVA(50 mg/kg/天)组。通过脱水、抑制前列腺素和一氧化氮合成以及暴露于造影剂(CM)诱导CIN。在诱导CIN后24小时和48小时测量血清肌酐(sCr)水平。在CM暴露48小时后,处死动物。检测肾组织中的基质金属蛋白酶(MMP)2(MMP - 2)、MMP - 9、肾损伤分子1(KIM - 1)和胱抑素C(Cys - C)。对肾组织进行组织病理学检查。所有治疗组的肾脏外观接近正常。与CIN组相比,所有治疗组在CIN诱导后48小时的sCr水平均有所下降。与CIN组相比,观察到MMP - 2、MMP - 9、KIM - 1和Cys - C水平显著下降。这些结果提供了新的证据,表明VAR和AVA可能具有预防CIN的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/628b/9144719/3749261771e7/jpm-12-00670-g001.jpg

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