N-乙酰半胱氨酸通过抑制 SIRT3 介导的线粒体功能障碍和细胞凋亡保护脓毒症急性肾损伤。

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Heng Fan, Jian-Wei Le, Min Sun, Jian-Hua Zhu
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引用次数: 0

摘要

研究目的研究N-乙酰半胱氨酸(NAC)通过调节Sirtuin3(SIRT3)介导的线粒体功能障碍和细胞凋亡对脓毒性急性肾损伤(SAKI)的保护作用:通过构建 SIRT3 基因敲除小鼠和培养肾小管上皮细胞(KTECs),我们评估了肾功能的变化并检测了腺嘌呤核苷酸转运体(ANT)的蛋白表达、并同时检测了toll样受体4(TLR4)、κB激酶抑制剂(IKKβ)、κBα抑制剂(IκBα)和p65蛋白的表达。我们用透射电子显微镜观察了KTEC的线粒体损伤,并用TdT介导的dUTP镍末端标记和流式细胞术评估了细胞凋亡:结果:SIRT3缺乏导致肾功能恶化,诱导型一氧化氮合酶生成显著增加,线粒体体积减少,TLR4、IκBα、IKKβ和p65蛋白上调,ANT、CypD和VDAC蛋白上调。然而,NAC能明显改善肾功能,并下调TLR4、IκBα、IKKβ和p65蛋白的表达。此外,SIRT3 缺乏导致 KTEC 细胞凋亡明显增加,而 NAC 可上调 SIRT3 的表达并抑制细胞凋亡:结论:通过抑制 SIRT3 介导的线粒体功能障碍和 KTEC 细胞凋亡,NAC 对 SAKI 有明显的保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
N-acetylcysteine protects septic acute kidney injury by inhibiting SIRT3-mediated mitochondrial dysfunction and apoptosis.

Objectives: To investigate the protective effect of N-acetylcysteine (NAC) on septic acute kidney injury (SAKI) via regulating Sirtuin3 (SIRT3)-mediated mitochondrial dysfunction and apoptosis.

Materials and methods: By constructing SIRT3 knockout mice and culturing kidney tubular epithelial cells (KTECs), we assessed the changes of renal function and detected the protein expression of adenine nucleotide translocator (ANT), cyclophilin (CypD) and voltage-dependent anion channel (VDAC) using western-blotting, and simultaneously detected toll-like receptor 4 (TLR4), inhibitor of kappa B kinase (IKKβ), inhibitor of Kappa Bα (IκBα), and p65 protein expression. We observed mitochondrial damage of KTECs using a transmission electron microscope and assessed apoptosis by TdT-mediated dUTP Nick-End Labeling and flow cytometry.

Results: SIRT3 deficiency led to the deterioration of renal function, and caused a significant increase in inducible nitric oxide synthase production, a decrease in mitochondrial volume, up-regulation of TLR4, IκBα, IKKβ, and p65 proteins, and up-regulation of ANT, CypD and VDAC proteins. However, NAC significantly improved renal function and down-regulated the expression of TLR4, IκBα, IKKβ, and p65 proteins. Furthermore, SIRT3 deficiency led to a significant increase in KTEC apoptosis, while NAC up-regulated the expression of SIRT3 and inhibited apoptosis.

Conclusion: NAC has a significant protective effect on SAKI by inhibiting SIRT3-mediated mitochondrial dysfunction and apoptosis of KTECs.

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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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