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用于研究疟疾相关急性肾损伤的新型实验小鼠模型

Novel Experimental Mouse Model to Study Malaria-Associated Acute Kidney Injury.

作者信息

Bensalel Johanna, Roberts Alexandra, Hernandez Kiara, Pina Angelica, Prempeh Winifred, Babalola Blessing V, Cannata Pablo, Lazaro Alberto, Gallego-Delgado Julio

机构信息

Department of Biological Sciences, Bronx, Lehman College, The City University of New York, New York, NY 10468, USA.

Ph.D. Program in Biology, The Graduate Center, The City University of New York, New York, NY 10016, USA.

出版信息

Pathogens. 2023 Apr 1;12(4):545. doi: 10.3390/pathogens12040545.

Abstract

The impact of malaria-associated acute kidney injury (MAKI), one of the strongest predictors of death in children with severe malaria (SM), has been largely underestimated and research in this area has been neglected. Consequently, a standard experimental mouse model to research this pathology is still lacking. The purpose of this study was to develop an in vivo model that resembles the pathology in MAKI patients. In this study, unilateral nephrectomies were performed on wild-type mice prior to infection with NK65. The removal of one kidney has shown to be an effective approach to replicating the most common findings in humans with MAKI. Infection of nephrectomized mice, compared to their non-nephrectomized counterparts, resulted in the development of kidney injury, evident by histopathological analysis and elevated levels of acute kidney injury (AKI) biomarkers, including urinary neutrophil gelatinase-associated lipocalin, serum Cystatin C, and blood urea nitrogen. Establishment of this in vivo model of MAKI is critical to the scientific community, as it can be used to elucidate the molecular pathways implicated in MAKI, delineate the development of the disease, identify biomarkers for early diagnosis and prognosis, and test potential adjunctive therapies.

摘要

疟疾相关急性肾损伤(MAKI)是重症疟疾(SM)患儿死亡的最强预测因素之一,其影响在很大程度上被低估,该领域的研究也一直被忽视。因此,仍缺乏用于研究这种病理状况的标准实验小鼠模型。本研究的目的是建立一种类似于MAKI患者病理状况的体内模型。在本研究中,在野生型小鼠感染NK65之前进行单侧肾切除术。切除一侧肾脏已被证明是复制MAKI患者最常见表现的有效方法。与未进行肾切除的对照小鼠相比,肾切除小鼠感染后出现了肾损伤,这通过组织病理学分析以及急性肾损伤(AKI)生物标志物水平升高得以证实,这些生物标志物包括尿中性粒细胞明胶酶相关脂质运载蛋白、血清胱抑素C和血尿素氮。建立这种MAKI体内模型对科学界至关重要,因为它可用于阐明MAKI涉及的分子途径、描绘疾病的发展过程、识别早期诊断和预后的生物标志物以及测试潜在的辅助治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/513e/10141210/67213473c35d/pathogens-12-00545-g001.jpg

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