Li Hai-Lun, Yan Zhuan, Ke Zun-Ping, Tian Xiao-Feng, Zhong Li-Li, Lin Yong-Tao, Xu Yong, Zheng Dong-Hui
Department of Nephrology, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu 223002, China.
Department of Emergency, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, China.
Oncotarget. 2018 Nov 27;9(93):36551-36560. doi: 10.18632/oncotarget.25663.
This study aims to determine whether insulin-like growth factor binding protein2 (IGFBP2) is a useful biomarker for early diagnosis of acute kidney injury (AKI), evaluate the therapeutic effects of resveratrol-loaded nanoparticles (Res-NPs), and investigate the possible underlying mechanisms in a rat model of AKI induced by IRI. Forty male Sprague-Dawley rats were randomly divided into four groups (10 animals per group): sham, IRI control, resveratrol, and Res-NPs injection. Kidney injury and the effects of Resveratrol and Res-NPs were determined by histological examination, renal function, cell apoptosis profile, and gene expression. Changes in IGFBP2 were similar with the pattern of well-known renal biomarkers, namely, kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin, in all groups. Compared with the IRI control and resveratrol groups, the Res-NPs groups displayed significantly reduced apoptotic rate, reactive oxygen species level, and malondialdehyde content, downregulated protein expression levels of and Bax with increased antioxidant glutathione peroxidase level, and upregulated expression of protein. Thus, IGFBP2 may serve as a promising novel biomarker of AKI, and Res-NPs may prevent kidney injury from ischemia/reperfusion in a rat model.
本研究旨在确定胰岛素样生长因子结合蛋白2(IGFBP2)是否为急性肾损伤(AKI)早期诊断的有用生物标志物,评估白藜芦醇负载纳米颗粒(Res-NPs)的治疗效果,并在缺血再灌注损伤(IRI)诱导的AKI大鼠模型中研究其可能的潜在机制。40只雄性Sprague-Dawley大鼠随机分为四组(每组10只动物):假手术组、IRI对照组、白藜芦醇组和Res-NPs注射组。通过组织学检查、肾功能、细胞凋亡情况和基因表达来确定肾损伤以及白藜芦醇和Res-NPs的作用。在所有组中,IGFBP2的变化与已知的肾脏生物标志物即肾损伤分子1和中性粒细胞明胶酶相关脂质运载蛋白的模式相似。与IRI对照组和白藜芦醇组相比,Res-NPs组的凋亡率、活性氧水平和丙二醛含量显著降低,Bax蛋白表达水平下调,抗氧化剂谷胱甘肽过氧化物酶水平升高,且 蛋白表达上调。因此,IGFBP2可能是一种有前景的新型AKI生物标志物,Res-NPs可能预防大鼠模型中缺血/再灌注引起的肾损伤。