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辣椒素对细胞焦亡和凋亡的抑制作用通过TRPV1/UCP2轴保护小鼠免受LPS诱导的急性肾损伤。

Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis .

作者信息

Han Jinrun, Wu Jinhao, Liu Hong, Huang Yu, Ju Wen, Xing Yifei, Zhang Xiaoping, Yang Jun

机构信息

The Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, Hubei, China.

The Intensive Care Unit, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Open Life Sci. 2023 Jul 29;18(1):20220647. doi: 10.1515/biol-2022-0647. eCollection 2023.

DOI:10.1515/biol-2022-0647
PMID:37528882
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10389676/
Abstract

Acute kidney injury is a fatal disease characterized by a rapid deterioration of kidney function. Capsaicin (-8-methyl--vanillyl-6-nonenamide) is a natural product extracted from . The aim of this study was to explore the protective effect of capsaicin on inflammation, apoptosis, and mitochondrial dysfunction in an model of acute kidney injury. Lipopolysaccharide (LPS)-induced acute kidney injury model was established in HK-2 cells to investigate the protective effect of capsaicin. Cell viability was assessed using CCK-8 assay, and protein expression was detected using western blot and immunofluorescence assay. Intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential were analyzed by flow cytometry. Cell apoptosis was detected by propidium iodide staining. The results showed that capsaicin ameliorated LPS-induced cytotoxicity and attenuated the release of interleukin (IL)-1β and IL-18. Intriguingly, genipin abolished the protective effect of capsaicin. Molecularly, capsaicin activated transient receptor potential cation channel subfamily V member 1 -mitochondrial uncoupling protein 2 axis and inhibited caspase-1-mediated pyroptosis. In addition, capsaicin alleviated LPS-induced ROS production and mitochondrial membrane potential disruption and inhibited apoptosis. These findings suggest that capsaicin shows a protective effect in acute kidney injury model.

摘要

急性肾损伤是一种以肾功能迅速恶化为特征的致命疾病。辣椒素(-8-甲基-香草基-6-壬酰胺)是从……中提取的天然产物。本研究的目的是探讨辣椒素在急性肾损伤模型中对炎症、细胞凋亡和线粒体功能障碍的保护作用。在HK-2细胞中建立脂多糖(LPS)诱导的急性肾损伤模型,以研究辣椒素的保护作用。使用CCK-8法评估细胞活力,使用蛋白质印迹法和免疫荧光法检测蛋白质表达。通过流式细胞术分析细胞内活性氧(ROS)水平和线粒体膜电位。通过碘化丙啶染色检测细胞凋亡。结果表明,辣椒素改善了LPS诱导的细胞毒性,并减弱了白细胞介素(IL)-1β和IL-18的释放。有趣的是,京尼平消除了辣椒素的保护作用。在分子水平上,辣椒素激活瞬时受体电位阳离子通道亚家族V成员1-线粒体解偶联蛋白2轴,并抑制半胱天冬酶-1介导的细胞焦亡。此外,辣椒素减轻了LPS诱导的ROS产生和线粒体膜电位破坏,并抑制了细胞凋亡。这些发现表明,辣椒素在急性肾损伤模型中具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/40fdfcf96973/j_biol-2022-0647-fig005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/bfb415eb625e/j_biol-2022-0647-ga001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/e2d655e894b9/j_biol-2022-0647-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/f1407cec6ff2/j_biol-2022-0647-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/5f24b84c0357/j_biol-2022-0647-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/fb556bc9e843/j_biol-2022-0647-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/40fdfcf96973/j_biol-2022-0647-fig005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/bfb415eb625e/j_biol-2022-0647-ga001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/e2d655e894b9/j_biol-2022-0647-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/f1407cec6ff2/j_biol-2022-0647-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/5f24b84c0357/j_biol-2022-0647-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/fb556bc9e843/j_biol-2022-0647-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d350/10389676/40fdfcf96973/j_biol-2022-0647-fig005.jpg

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