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禁食可恢复大鼠与年龄相关的高血压:重置肾素-血管紧张素系统成分和klotho蛋白。

Fasting recovers age-related hypertension in the rats: reset of renal renin-angiotensin system components and klotho.

作者信息

Badreh Firuzeh, Joukar Siyavash, Badavi Mohammad, Rashno Mohammad

机构信息

Behbahan Faculty of Medical Sciences, Behbahan, Iran.

Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

BMC Nephrol. 2024 Dec 23;25(1):470. doi: 10.1186/s12882-024-03918-y.

DOI:10.1186/s12882-024-03918-y
PMID:39716128
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11667979/
Abstract

BACKGROUND

The renal renin-angiotensin system (RAS) plays a vital part in the control of blood pressure and is known to be affected by aging. This study aimed to investigate the effects of intermittent fasting on age-related hypertension and the expression of local renal RAS components.

METHODS

The Wistar rats were categorized into three main age groups (young, middle aged, and elderly) and three dietary treatment models, including ad libitum feeding (AL), every other day fasting (EOD), and one day per week of fasting (FW). After three months, blood pressure (BP) was assessed. Some genes and proteins of the renal RAS system were measured by using Real time PCR and Western blot. α-klotho and Ang II proteins were assessed by ELISA method.

RESULTS

Old rats exhibited significantly increase in BP and Ang II (P < 0.001 vs. young rats) and a significant reduction in circulating levels of α-klotho and kidney AT2R protein (P < 0.001, P < 0.01, vs. young rats, respectively). Additionally, they respond to aging by increasing the AT1aR/AT2R proteins ratio (P < 0.05). Two model of feeding reduced BP in old rats and circulating Ang II in middle-aged and older rats. Moreover, by fasting, ACE2 protein expression was elevated in old rats. EOD fasting also significantly elevated the AT2 receptor protein and reduced the AT1aR/AT2R proteins ratio in the older rats (P < 0.001, P < 0.01, respectively).

CONCLUSION

Our findings suggest that fasting, particularly EOD, can attenuate age-related hypertension, partly through reset of the local renal RAS and increase of klotho protein expression.

摘要

背景

肾脏肾素-血管紧张素系统(RAS)在血压控制中起着至关重要的作用,并且已知会受到衰老的影响。本研究旨在探讨间歇性禁食对年龄相关性高血压以及肾脏局部RAS成分表达的影响。

方法

将Wistar大鼠分为三个主要年龄组(年轻、中年和老年)以及三种饮食处理模式,包括自由进食(AL)、隔日禁食(EOD)和每周禁食一天(FW)。三个月后,评估血压(BP)。使用实时PCR和蛋白质印迹法检测肾脏RAS系统的一些基因和蛋白质。通过ELISA法评估α-klotho和Ang II蛋白。

结果

老年大鼠的血压和Ang II显著升高(与年轻大鼠相比,P < 0.001),循环中的α-klotho水平和肾脏AT2R蛋白显著降低(分别与年轻大鼠相比,P < 0.001,P < 0.01)。此外,它们通过增加AT1aR/AT2R蛋白比率来应对衰老(P < 0.05)。两种喂养模式降低了老年大鼠的血压以及中年和老年大鼠循环中的Ang II。此外,通过禁食,老年大鼠的ACE2蛋白表达升高。隔日禁食还显著提高了老年大鼠的AT2受体蛋白水平,并降低了AT1aR/AT2R蛋白比率(分别为P < 0.001,P < 0.01)。

结论

我们的研究结果表明,禁食,尤其是隔日禁食,可以减轻年龄相关性高血压,部分是通过重置肾脏局部RAS和增加klotho蛋白表达来实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/9840519bee75/12882_2024_3918_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/e3ab7752c93e/12882_2024_3918_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/0914001110a3/12882_2024_3918_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/2db8ab4626ee/12882_2024_3918_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/154613174139/12882_2024_3918_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/9840519bee75/12882_2024_3918_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/e3ab7752c93e/12882_2024_3918_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/0914001110a3/12882_2024_3918_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/2db8ab4626ee/12882_2024_3918_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/154613174139/12882_2024_3918_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc3/11667979/9840519bee75/12882_2024_3918_Fig5_HTML.jpg

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