Escuela Militar de Medicina, Centro Militar de Ciencias de la Salud, Secretaria de la Defensa Nacional, Ciudad de México 11200, Mexico.
Facultad de Estudios Superiores de Cuautitlán, Universidad Nacional Autónoma de México, Estado de México 54740, Mexico.
Oxid Med Cell Longev. 2019 Mar 14;2019:5420624. doi: 10.1155/2019/5420624. eCollection 2019.
The acute kidney injury (AKI) is characterized by a sudden glomerular filtration reduction. Renal or intrinsic causes of AKI include nephrotoxicity induced by exogenous agents like cisplatin, which causes oxidative stress altering the biochemical process and leading to apoptosis. Therefore, this research is aimed at analyzing the embryonic stem cells (ESC) nephroprotective effect in AKI induced by cisplatin, employing genetic, phenotypic, and microspectroscopic techniques.
Thirty mice were randomly divided into three groups ( = 10): the healthy, isotonic salt solution (ISS), and mouse embryonic stem cells (mESC) groups. The ISS and mESC groups were subjected to AKI using cisplatin; 24 h post-AKI received an intraperitoneal injection of ISS or 1 × 10 mESC, respectively. At days 4 and 8 post-AKI, five mice of each group were sacrificed to analyze the histopathological, genetic ( and ), protein (p53), and vibrational microspectroscopic changes.
Histopathologically, interstitial nephritis and acute tubular necrosis were observed; however, the mESC group showed a more preserved microarchitecture with high cellularity. Additionally, the PDK4 and HO-1 gene expression only increased in the ISS group on day 4 post-AKI. Likewise, p53 was more immunoexpressed at day 8 post-AKI in the ISS group. About biomolecular analysis by microspectroscopy, bands associated with lipids, proteins, and nucleic acids were evidenced. Besides, ratios related to membrane function (protein/lipid), unsaturated lipid content (olefinic/total lipid, olefinic/total CH, and CH/CH), and lipid peroxidation demonstrated oxidative stress induction and lipid peroxidation increase mainly in the ISS group. Finally, the principal component analysis discriminated against each group; nonetheless, some data of the healthy and mESC groups at day 8 were correlated.
The mESC implant diminishes cisplatin nephrotoxicity, once the protective effect in the reduction of lipid peroxidation was demonstrated, reflecting a functional and histological restoration.
急性肾损伤（AKI）的特征是肾小球滤过率突然降低。AKI 的肾内或固有原因包括顺铂等外源性药物引起的肾毒性，其导致氧化应激改变生化过程并导致细胞凋亡。因此，本研究旨在通过遗传、表型和微光谱技术分析胚胎干细胞（ESC）在顺铂诱导的 AKI 中的肾保护作用。
将 30 只小鼠随机分为三组（每组 10 只）：健康组、等渗盐溶液（ISS）组和小鼠胚胎干细胞（mESC）组。ISS 和 mESC 组通过顺铂诱导 AKI；AKI 后 24 小时分别给予 ISS 或 1×10 mESC 腹腔注射。AKI 后第 4 天和第 8 天，每组处死 5 只小鼠，分析组织病理学、遗传（和）、蛋白（p53）和振动微光谱变化。
组织病理学观察到间质性肾炎和急性肾小管坏死，但 mESC 组显示出更保存的微结构和更高的细胞密度。此外，PDK4 和 HO-1 基因表达仅在 AKI 后第 4 天的 ISS 组中增加。同样，ISS 组在 AKI 后第 8 天 p53 的免疫表达更高。关于通过微光谱分析的生物分子分析，证实了与脂质、蛋白质和核酸相关的带。此外，与膜功能（蛋白质/脂质）、不饱和脂质含量（烯键/总脂质、烯键/总 CH 和 CH/CH）相关的比率表明氧化应激诱导和脂质过氧化增加主要发生在 ISS 组。最后，主成分分析区分了每个组；然而，第 8 天健康组和 mESC 组的一些数据相关。
mESC 移植可减轻顺铂的肾毒性，因为已证明在减少脂质过氧化方面具有保护作用，反映了功能和组织学的恢复。
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