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中性粒细胞明胶酶相关脂质运载蛋白和铁稳态在老年脓毒症幸存者大鼠物体识别障碍中的作用。

The role of neutrophil gelatinase-associated lipocalin and iron homeostasis in object recognition impairment in aged sepsis-survivor rats.

机构信息

Department of Frailty Research and Prevention, Hirosaki University Graduate School of Medicine, Hirosaki, 0368562, Japan.

Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki, 0368562, Japan.

出版信息

Sci Rep. 2022 Jan 7;12(1):249. doi: 10.1038/s41598-021-03981-7.

DOI:10.1038/s41598-021-03981-7
PMID:34997032
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8742111/
Abstract

Older adult patients with sepsis frequently experience cognitive impairment. The roles of brain neutrophil gelatinase-associated lipocalin (NGAL) and iron in older sepsis patients remain unknown. We investigated the effects of lipopolysaccharide-induced sepsis on novel object recognition test, NGAL levels, an inflammatory mediator tumor necrosis factor-α (TNFα) levels, and iron ion levels in the hippocampus and cortex of young and aged rats. The effect of an iron chelator deferoxamine pretreatment on aged sepsis rats was also examined. Young sepsis-survivor rats did not show impaired novel object recognition, TNFα responses, or a Fe/Fe imbalance. They showed hippocampal and cortical NGAL level elevations. Aged sepsis-survivor rats displayed a decreased object discrimination index, elevation of NGAL levels and Fe/Fe ratio, and no TNFα responses. Pretreatment with deferoxamine prevented the reduction in the object recognition of aged sepsis-survivor rats. The elevation in hippocampal and cortical NGAL levels caused by lipopolysaccharide was not influenced by deferoxamine pretreatment. The lipopolysaccharide-induced Fe/Fe ratio elevation was blocked by deferoxamine pretreatment. In conclusion, our findings suggest that iron homeostasis in the cortex and hippocampus contributes to the maintenance of object recognition ability in older sepsis survivors.

摘要

老年脓毒症患者常伴有认知功能障碍。脑中性粒细胞明胶酶相关载脂蛋白（NGAL）和铁在老年脓毒症患者中的作用尚不清楚。我们研究了脂多糖诱导的脓毒症对年轻和老年大鼠海马和皮质中新物体识别测试、NGAL 水平、炎症介质肿瘤坏死因子-α（TNFα）水平和铁离子水平的影响。还研究了铁螯合剂去铁胺预处理对老年脓毒症大鼠的影响。年轻脓毒症幸存者大鼠没有表现出新物体识别、TNFα 反应或铁失衡受损。它们表现出海马和皮质中 NGAL 水平升高。老年脓毒症幸存者大鼠表现出物体辨别指数降低、NGAL 水平和 Fe/Fe 比值升高，以及没有 TNFα 反应。去铁胺预处理可防止老年脓毒症幸存者大鼠的物体识别能力下降。脂多糖诱导的海马和皮质 NGAL 水平升高不受去铁胺预处理的影响。去铁胺预处理可阻断脂多糖诱导的 Fe/Fe 比值升高。总之，我们的研究结果表明，皮质和海马中的铁平衡有助于维持老年脓毒症幸存者的物体识别能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/9b89c64c4521/41598_2021_3981_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/616389e23089/41598_2021_3981_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/9e2b5bd78ff6/41598_2021_3981_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/40d2de7fe1d7/41598_2021_3981_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/984f40e7d938/41598_2021_3981_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/9b89c64c4521/41598_2021_3981_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/616389e23089/41598_2021_3981_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/9e2b5bd78ff6/41598_2021_3981_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/40d2de7fe1d7/41598_2021_3981_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/984f40e7d938/41598_2021_3981_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1224/8742111/9b89c64c4521/41598_2021_3981_Fig5_HTML.jpg

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