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硫氧还蛋白通过减轻炎症、氧化应激和细胞凋亡来缓解小鼠脂多糖诱导的急性肾损伤。

Thioredoxin relieves lipopolysaccharide-induced acute kidney injury in mice by reducing inflammation, oxidative stress and apoptosis.

作者信息

Wang Jingjing, Zhang Wenjuan, Lu Guoyuan

机构信息

Department of Nephrology, Changzhou Fourth People's Hospital, Changzhou, Jiangsu 213000, P.R. China.

Department of Nephrology, First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215000, P.R. China.

出版信息

Exp Ther Med. 2021 Jun;21(6):629. doi: 10.3892/etm.2021.10061. Epub 2021 Apr 15.

DOI:10.3892/etm.2021.10061
PMID:33936285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8082584/
Abstract

Acute kidney injury (AKI) is a serious disease with rapid onset and a high mortality rate. It is therefore particularly important to identify a suitable method for treating AKI. Thioredoxin (Trx) is a potent anti-inflammatory and anti-oxidant protein that is prevalent in living organisms. The aim of the present study was to facilitate the clinical treatment of AKI via the study of Trx. Lipopolysaccharide (LPS) was used to construct an AKI model in mice and the mice were pre-treated with Trx to examine its effect on AKI. In addition, human renal tubular epithelial HK-2 cells were cultured and stimulated with Trx to examine its effect on inflammation, levels of oxidative stress and apoptosis in the HK-2 cells. The NF-κB signaling pathway is a classical inflammation-related pathway and the mechanism of Trx was investigated by evaluating the association between Trx and the NF-κB signaling pathway. Trx treatment reduced LPS-induced levels of inflammation, oxidative stress and apoptosis in the HK-2 cells. The activity of NF-κB signaling pathway was increased in LPS-induced HK-2 cells, while Trx treatment effectively reduced NF-κB signaling pathway activity. In addition, Trx treatment significantly reduced LPS-induced mouse AKI , which was characterized by a decrease in inflammatory factors in mouse serum, a decrease in AKI-associated molecules in mouse urine and a decrease in oxidative stress levels in mouse kidney tissue samples. Trx treatment reduced inflammation, levels of oxidative stress and apoptosis in HK-2 cells by inhibiting the NF-κB signaling pathway, thereby alleviating LPS-induced mouse AKI.

摘要

急性肾损伤(AKI)是一种起病迅速且死亡率高的严重疾病。因此,确定一种合适的AKI治疗方法尤为重要。硫氧还蛋白(Trx)是一种在生物体中普遍存在的强效抗炎和抗氧化蛋白。本研究的目的是通过对Trx的研究促进AKI的临床治疗。使用脂多糖(LPS)构建小鼠AKI模型,并对小鼠进行Trx预处理以检查其对AKI的影响。此外,培养人肾小管上皮HK-2细胞并用Trx刺激,以检查其对HK-2细胞炎症、氧化应激水平和细胞凋亡的影响。NF-κB信号通路是一条经典的炎症相关通路,通过评估Trx与NF-κB信号通路之间的关联来研究Trx的作用机制。Trx处理降低了LPS诱导的HK-2细胞中的炎症、氧化应激和细胞凋亡水平。在LPS诱导的HK-2细胞中,NF-κB信号通路的活性增加,而Trx处理有效地降低了NF-κB信号通路的活性。此外,Trx处理显著减轻了LPS诱导的小鼠AKI,其特征为小鼠血清中炎症因子减少、小鼠尿液中AKI相关分子减少以及小鼠肾组织样本中氧化应激水平降低。Trx处理通过抑制NF-κB信号通路降低了HK-2细胞中的炎症、氧化应激和细胞凋亡水平,从而减轻了LPS诱导的小鼠AKI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/7761d3dd93aa/etm-21-06-10061-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/b14edb164a04/etm-21-06-10061-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/a6140c823d2d/etm-21-06-10061-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/073fcee4c43d/etm-21-06-10061-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/e79689f652a3/etm-21-06-10061-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/7761d3dd93aa/etm-21-06-10061-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/b14edb164a04/etm-21-06-10061-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/a6140c823d2d/etm-21-06-10061-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/073fcee4c43d/etm-21-06-10061-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/e79689f652a3/etm-21-06-10061-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ded/8082584/7761d3dd93aa/etm-21-06-10061-g04.jpg

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