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

Novel Experimental Mouse Model to Study Malaria-Associated Acute Kidney Injury.
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DOI:
10.3390/pathogens12040545
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发表时间:
2023-04-01
期刊:
Pathogens (Basel, Switzerland)
影响因子:
--
通讯作者:
Gallego-Delgado J
Gallego-Delgado J
中科院分区:
其他
文献类型:
--
作者:
Bensalel J;Roberts A;Hernandez K;Pina A;Prempeh W;Babalola BV;Cannata P;Lazaro A;Gallego-Delgado J

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疟疾相关急性肾损伤(MAKI)是严重疟疾(SM)儿童死亡的最强预测因子之一,其影响在很大程度上被低估,该领域的研究也被忽视。因此,研究这种病理学的标准实验小鼠模型仍然缺乏。本研究的目的是开发一种类似于MAKI患者病理学的体内模型。在这项研究中,单侧肾切除术进行野生型小鼠感染伯氏疟原虫NK65之前。切除一个肾脏已被证明是复制MAKI患者最常见结果的有效方法。肾切除小鼠的感染,与其非肾切除的对应物相比,导致肾损伤的发展,通过组织病理学分析和急性肾损伤(阿基)生物标志物水平升高来证明,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。MAKI体内模型的建立对科学界至关重要,因为它可用于阐明MAKI中涉及的分子途径,描述疾病的发展,鉴定用于早期诊断和预后的生物标志物,以及测试潜在的预防性治疗。
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 Plasmodium berghei 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.
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