外源性spexin加重肾缺血再灌注损伤并触发健康肾脏的毒性。

IF 3.5 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Kadri Kulualp, Meltem Kumaş Kulualp, Zeynep Semen, Gökçen Güvenç Bayram, Aslı Çelik, Melek Yeşim Ak, Osman Yilmaz
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引用次数: 0

摘要

肾缺血再灌注损伤(IRI)是急性肾损伤(AKI)的主要原因,导致大量的发病率和死亡率。SPX是一种由14个氨基酸组成的内源性肽,参与代谢调节和免疫调节,尚未在慢性治疗和肾IRI的背景下进行研究。本研究评估了外源性SPX对iri诱导的损伤和健康肾脏的肾功能、组织病理变化和分子通路的影响。将28只雄性BALB/c小鼠分为对照组、SPX组、IRI组和SPX+IRI组。双侧肾缺血30分钟,再灌注6小时,诱导IRI。分析肾损伤标志物、组织病理学改变、炎症介质、凋亡标志物和纤维化相关蛋白。SPX通过激活Wnt/β-catenin信号通路,促进促炎、促凋亡和促纤维化介质的上调,显著加重了iri诱导的肾损伤。值得注意的是,与在iri诱导的损伤肾脏中观察到的相比,SPX在健康肾脏中产生了更严重的有害肾毒性作用。这些发现表明,SPX慢性治疗可能具有内在的促炎、促凋亡和纤维化特性,引起了人们对其治疗潜力的关注。需要进一步的研究来阐明其在肾脏疾病中的生理作用和治疗意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exogenous spexin aggravates renal ischemia reperfusion injury and triggers toxicity in healthy kidneys.

Renal ischemia-reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI), leading to substantial morbidity and mortality. Spexin (SPX), a 14-amino acid endogenous peptide involved in metabolic regulation and immune modulation, has not yet been studied in the context of chronic treatment and renal IRI. This study evaluated the effects of exogenous SPX on renal function, histopathological changes, and molecular pathways in both IRI-induced injured and healthy kidneys. Twenty-eight male BALB/c mice were divided into four groups: control, SPX, IRI, and SPX+IRI. IRI was induced by 30 minutes of bilateral renal ischemia followed by 6 hours of reperfusion. Renal injury markers, histopathological changes, inflammatory mediators, apoptotic markers, and fibrosis-related proteins were analyzed. SPX significantly exacerbated IRI-induced kidney injury by activating the Wnt/β-catenin signaling pathway and promoting the upregulation of pro-inflammatory, pro-apoptotic, and pro-fibrotic mediators. It is noteworthy that SPX exerted more severe deleterious nephrotoxic effects in the healthy kidney compared to those observed in the IRI-induced injured kidney. These findings indicate that chronic treatment with SPX administration may have intrinsic pro-inflammatory, pro-apoptotic and fibrotic properties, raising concerns about its therapeutic potential. Further research is needed to clarify its physiological role and therapeutic implications in kidney diseases.

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来源期刊
Frontiers of Medicine
Frontiers of Medicine ONCOLOGYMEDICINE, RESEARCH & EXPERIMENTAL&-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
18.30
自引率
0.00%
发文量
800
期刊介绍: Frontiers of Medicine is an international general medical journal sponsored by the Ministry of Education of China. The journal is jointly published by the Higher Education Press and Springer. Since the first issue of 2010, this journal has been indexed in PubMed/MEDLINE. Frontiers of Medicine is dedicated to publishing original research and review articles on the latest advances in clinical and basic medicine with a focus on epidemiology, traditional Chinese medicine, translational research, healthcare, public health and health policies.
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