恩帕列嗪通过减少sirt1介导的氧化应激来改善D-半乳糖诱导的肾脏衰老。

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY Biogerontology Pub Date : 2023-10-01 Epub Date: 2023-05-25 DOI:10.1007/s10522-023-10038-x
Ronghua Fang, Jie Chen, Jiangchuan Long, Binghan Zhang, Qixuan Huang, Shengbing Li, Ke Li, Qing Chen, Dongfang Liu
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引用次数: 0

摘要

钠-葡萄糖协同转运蛋白-2(SGLT-2)抑制剂因其对肾脏的显著保护作用而受到广泛关注。先前的研究表明,Sirt1作为一种抗衰老蛋白,与氧化还原稳态的维持密切相关。本研究的目的是确定恩帕列嗪是否能改善D-半乳糖诱导的小鼠肾脏衰老,并探讨Sirt1的可能机制。我们通过给药D-半乳糖构建了小鼠快速衰老模型。通过用高糖处理细胞来构建衰老模型。跑步机和Y迷宫测试用于评估运动耐受性和学习记忆能力。病理染色切片用于评估肾损伤。通过衰老相关的β-半乳糖苷酶染色评估组织和细胞衰老。免疫印迹法检测P16、SOD1、SOD2和Sirt1的表达水平。通过行为测试和衰老标志物蛋白质水平测量,D-半乳糖处理的小鼠表现出显著的年龄相关性变化。恩帕列嗪减轻了这些衰老症状。此外,模型小鼠的Sirt1、SOD1和SOD2水平下调,恩帕列嗪治疗上调。恩帕列嗪在细胞水平上具有类似的保护作用,并且这些作用被Sirt1抑制剂降低。恩帕列嗪具有抗衰老作用,这可能与减少Sirt1介导的氧化应激有关。
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Empagliflozin improves kidney senescence induced by D-galactose by reducing sirt1-mediated oxidative stress.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have received widespread attention because of their significant protective effects on the kidney. Previous studies have shown that Sirt1, as which is an antiaging protein, is closely related to the maintenance of redox homeostasis. The goal of this study was to determine whether empagliflozin could ameliorate D-galactose-induced renal senescence in mice, and examine the possible mechanisms of Sirt1. We constructed a rapid ageing model in mice by administering D-galactose. An ageing model was constructed by treating cells with high glucose. Treadmill and Y-maze tests were used to assess exercise tolerance and learning memory ability. Pathologically stained sections were used to assess kidney injury. Tissue and cell senescence were evaluated by senescence-associated β-galactosidase staining. The expression levels of P16, SOD1, SOD2 and Sirt1 were detected by immunoblotting. D-gal-treated mice exhibited significant age-related changes, as measured by behavioural tests and ageing marker protein levels. empagliflozin alleviated these ageing manifestations. In addition, Sirt1, SOD1 and SOD2 levels were downregulated in model mice and upregulated by empagliflozin treatment. Empagliflozin had similar protective effects at the cellular level, and these effects were reduced by the Sirt1 inhibitor. Empagliflozin has an antiaging effect, which may be related to reducing Sirt1-mediated oxidative stress.

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来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
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