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热量限制通过 SIRT1/GPX4 激活来预防对比剂诱导的肾病。

Calorie Restriction Protects against Contrast-Induced Nephropathy via SIRT1/GPX4 Activation.

机构信息

Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.

Chongqing Institute of Cardiology& Chongqing Key Laboratory of Hypertension Research, Chongqing, China.

出版信息

Oxid Med Cell Longev. 2021 Oct 19;2021:2999296. doi: 10.1155/2021/2999296. eCollection 2021.

DOI:10.1155/2021/2999296
PMID:34712381
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8548166/
Abstract

Calorie restriction (CR) extends lifespan and increases resistance to multiple forms of stress, including renal ischemia-reperfusion (I/R) injury. However, whether CR has protective effects on contrast-induced nephropathy (CIN) remains to be determined. In this study, we evaluated the therapeutic effects of CR on CIN and investigated the potential mechanisms. CIN was induced by the intravenous injection of iodinated contrast medium (CM) iopromide (1.8 g/kg) into Sprague Dawley rats with normal food intake or 40% reduced food intake, 4 weeks prior to iopromide administration. We found that CR was protective of CIN, assessed by renal structure and function. CM increased apoptosis, reactive oxygen species (ROS), and inflammation in the renal outer medulla, which were decreased by CR. The silent information regulator 1 (SIRT1) participated in the protective effect of CR on CIN, by upregulating glutathione peroxidase 4 (GPX4), a regulator of ferroptosis, because this protective effect was reversed by EX527, a specific SIRT1 antagonist. Our study showed that CR protected CIN via SIRT1/GPX4 activation. CR may be used to mitigate CIN.

摘要

热量限制(CR)可延长寿命并增强对多种形式的应激的抵抗力,包括肾缺血再灌注(I/R)损伤。然而,CR 是否对造影剂肾病(CIN)具有保护作用仍有待确定。在这项研究中,我们评估了 CR 对 CIN 的治疗作用,并研究了其潜在机制。在给予碘普罗胺(1.8 g/kg)静脉注射之前的 4 周,通过正常饮食或 40%减少饮食摄入的方式将碘普罗胺诱导到 Sprague Dawley 大鼠中,以诱导 CIN。我们发现 CR 通过肾脏结构和功能保护 CIN。CM 增加了肾外髓质中的细胞凋亡、活性氧(ROS)和炎症,而 CR 则降低了这些物质。沉默信息调节因子 1(SIRT1)通过上调谷胱甘肽过氧化物酶 4(GPX4)参与了 CR 对 CIN 的保护作用,GPX4 是铁死亡的调节剂,因为这种保护作用被特定的 SIRT1 拮抗剂 EX527 逆转。我们的研究表明,CR 通过 SIRT1/GPX4 的激活来保护 CIN。CR 可能被用于减轻 CIN。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/9e1f498cb147/OMCL2021-2999296.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/4d013be0b3f4/OMCL2021-2999296.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/14162dc0e083/OMCL2021-2999296.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/a680d6136236/OMCL2021-2999296.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/ea6fabb087f7/OMCL2021-2999296.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/935f704a03cd/OMCL2021-2999296.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/9e1f498cb147/OMCL2021-2999296.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/4d013be0b3f4/OMCL2021-2999296.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/14162dc0e083/OMCL2021-2999296.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/a680d6136236/OMCL2021-2999296.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/ea6fabb087f7/OMCL2021-2999296.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/935f704a03cd/OMCL2021-2999296.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9ca/8548166/9e1f498cb147/OMCL2021-2999296.006.jpg

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