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造影剂联合急性心肌缺血再灌注手术诱导急性肾损伤的临床前模型的建立与评估

Establishment and assessment of a preclinical model of acute kidney injury induced by contrast media combined acute myocardial ischemia reperfusion surgery.

作者信息

Yu Sijia, Dong Xiaoli, Lai Wenguang, Lu Hongyu, Xie Yun, Xu Jun-Yan, Zeng Yewen, Han Kedong, Liang Jinqiang, Liu Jin, Liu Yong, Chen Jiyan

机构信息

Department of Cardiology, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.

出版信息

Exp Ther Med. 2023 May 15;26(1):321. doi: 10.3892/etm.2023.12020. eCollection 2023 Jul.

Abstract

Acute kidney injury (AKI) is a common complication after acute myocardial infarction (AMI) in clinical practice, and the majority of previous preclinical models were induced by a single factor. The objective of the present study was to establish a stable preclinic model of AKI induced by contrast media (CM) with acute myocardial ischemia reperfusion surgery and to identify the effect of oxidative stress on kidney injury. Rats were treated individually or with CM or myocardial ischemia reperfusion surgery. Renal baseline and AKI parameters, the level of oxidative stress and histopathological images were examined along with AKI biomarkers. Results showed the incidence of AKI in the CM group and ischemia reperfusion injury (IRI) group was 40%, χ test (P<0.05 vs. CM-IRI) and 35%, χ test (P<0.05 vs. CM-IRI) and the combination group had the highest incidence rate 75%. IRI surgery combined with CM diminished kidney function and induced oxidative stress by increasing creatinine, blood urea nitrogen and reactive oxygen species levels. Western blotting showed that the early AKI biomarker of NGAL and KIM-1 increased and that the combination group had the highest value. Pathology damage exhibited severe kidney damage in the combination group compared with other control groups. The present research established a reliable preclinic model of post-AMI AKI with a stable and high postoperative AKI rate. Additionally, CM was demonstrated to exacerbate AKI caused by acute myocardial infarction through oxidative stress and, thus, oxidative stress may be a potential therapeutic target.

摘要

急性肾损伤(AKI)是临床实践中急性心肌梗死(AMI)后常见的并发症,且大多数既往临床前模型是由单一因素诱导的。本研究的目的是通过对比剂(CM)联合急性心肌缺血再灌注手术建立稳定的临床前AKI模型,并确定氧化应激对肾损伤的影响。将大鼠单独或用CM或进行心肌缺血再灌注手术处理。检测了肾脏基线和AKI参数、氧化应激水平及组织病理学图像,同时检测了AKI生物标志物。结果显示,CM组和缺血再灌注损伤(IRI)组的AKI发生率分别为40%(χ检验,与CM-IRI组相比P<0.05)和35%(χ检验,与CM-IRI组相比P<0.05),联合组的发生率最高,为75%。IRI手术联合CM降低了肾功能,并通过增加肌酐、血尿素氮和活性氧水平诱导了氧化应激。蛋白质印迹法显示,早期AKI生物标志物中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和肾损伤分子-1(KIM-1)增加,联合组的值最高。与其他对照组相比,联合组的病理学损伤表现为严重的肾损伤。本研究建立了一种可靠的AMI后AKI临床前模型,术后AKI发生率稳定且高。此外,已证明CM通过氧化应激加剧急性心肌梗死所致的AKI,因此,氧化应激可能是一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/649f/10280325/2c506e3ddd36/etm-26-01-12020-g00.jpg

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