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鞣花酸通过上调 SIRT1 和 NRF2 改善衰老引起的肾脏氧化损伤。

Ellagic acid ameliorates aging-induced renal oxidative damage through upregulating SIRT1 and NRF2.

机构信息

Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

BMC Complement Med Ther. 2023 Mar 10;23(1):77. doi: 10.1186/s12906-023-03907-y.

DOI:10.1186/s12906-023-03907-y
PMID:36899375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9999491/
Abstract

BACKGROUND

Aging is associated with impaired renal function and structural alterations. Oxidative stress plays a vital role in renal senescence and damage. Sirtuin 1 (SIRT1) is thought to protect cells from oxidative stress through nuclear factor erythroid 2-related factor 2 (NRF2). Ellagic acid (EA), a natural antioxidant, has been demonstrated to have renoprotective roles in vitro and in vivo. This study investigated if SIRT1 and NRF2 mediate the protective effects of EA in aged kidneys.

METHODS

Male Wistar rats were divided into three groups including young (4 months), old, and old + EA (25 months). Young and old groups received EA solvent, while the old + EA group was treated with EA (30 mg/kg) by gavage for 30 days. Then, the level of renal oxidative stress, SIRT1 and NRF2 expression, kidney function parameters, and histopathological indices were measured.

RESULTS

Treatment with EA significantly increased the level of antioxidant enzymes and reduced malondialdehyde concentration (P < 0.01). Moreover, EA administration remarkably upregulated mRNA and protein levels of SIRT1 and NRF2 as well as deacetylated NRF2 protein (P < 0.05). Additionally, EA treated rats improved kidney function and histopathological scores (P < 0.05).

CONCLUSIONS

These findings suggest that ellagic acid exerts protective effects on aged kidneys by activating SIRT1 and NRF2 signaling.

摘要

背景

衰老与肾功能受损和结构改变有关。氧化应激在肾脏衰老和损伤中起着至关重要的作用。Sirtuin 1(SIRT1)被认为通过核因子红细胞 2 相关因子 2(NRF2)来保护细胞免受氧化应激。鞣花酸(EA)是一种天然抗氧化剂,已被证明在体外和体内具有肾脏保护作用。本研究探讨了 SIRT1 和 NRF2 是否介导 EA 对老年肾脏的保护作用。

方法

雄性 Wistar 大鼠分为三组,包括年轻组(4 个月)、老年组和老年+EA 组(25 个月)。年轻组和老年组给予 EA 溶剂,老年+EA 组给予 EA(30mg/kg)灌胃 30 天。然后,测量肾脏氧化应激水平、SIRT1 和 NRF2 表达、肾功能参数和组织病理学指标。

结果

EA 治疗显著增加了抗氧化酶的水平并降低了丙二醛浓度(P<0.01)。此外,EA 给药还显著上调了 SIRT1 和 NRF2 的 mRNA 和蛋白水平以及去乙酰化的 NRF2 蛋白(P<0.05)。此外,EA 处理的大鼠改善了肾功能和组织病理学评分(P<0.05)。

结论

这些发现表明,鞣花酸通过激活 SIRT1 和 NRF2 信号通路对老年肾脏发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/9999491/8953f6f6bdfa/12906_2023_3907_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/9999491/d4031f6d7e96/12906_2023_3907_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/9999491/460d6c055f5b/12906_2023_3907_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/9999491/03e1b4cea397/12906_2023_3907_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/9999491/8953f6f6bdfa/12906_2023_3907_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/9999491/d4031f6d7e96/12906_2023_3907_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/9999491/460d6c055f5b/12906_2023_3907_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/9999491/03e1b4cea397/12906_2023_3907_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d64e/9999491/8953f6f6bdfa/12906_2023_3907_Fig4_HTML.jpg

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