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骨化三醇可改善高盐饮食诱导的高血压损伤:与肠道-肾脏轴相互作用的证据。

Calcitriol ameliorates damage in high-salt diet-induced hypertension: Evidence of communication with the gut-kidney axis.

机构信息

School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.

Department of Cardiology, Zhongshan Hospital of Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China.

出版信息

Exp Biol Med (Maywood). 2022 Apr;247(8):624-640. doi: 10.1177/15353702211062507. Epub 2021 Dec 11.

Abstract

Several studies have established a link between high-salt diet, inflammation, and hypertension. Vitamin D supplementation has shown anti-inflammatory effects in many diseases; gut microbiota is also associated with a wide variety of cardiovascular diseases, but potential role of vitamin D and gut microbiota in high-salt diet-induced hypertension remains unclear. Therefore, we used rats with hypertension induced by a high-salt diet as the research object and analyzed the transcriptome of their tissues (kidney and colon) and gut microbiome to conduct an overall analysis of the gut-kidney axis. We aimed to confirm the effects of high salt and calcitriol on the gut-kidney immune system and the composition of the intestinal flora. We demonstrate that consumption of a high-salt diet results in hypertension and inflammation in the colon and kidney and alteration of gut microbiota composition and function. High-salt diet-induced hypertension was found to be associated with seven microbial taxa and mainly associated with reduced production of the protective short-chain fatty acid butyrate. Calcitriol can reduce colon and kidney inflammation, and there are gene expression changes consistent with restored intestinal barrier function. The protective effect of calcitriol may be mediated indirectly by immunological properties. Additionally, the molecular pathways of the gut microbiota-mediated blood pressure regulation may be related to circadian rhythm signals, which needs to be further investigated. An innovative association analysis of the microbiota may be a key strategy to understanding the association between gene patterns and host.

摘要

多项研究已经证实,高盐饮食、炎症和高血压之间存在关联。维生素 D 补充剂已在许多疾病中显示出抗炎作用;肠道微生物群也与多种心血管疾病有关,但维生素 D 和肠道微生物群在高盐饮食诱导的高血压中的潜在作用尚不清楚。因此,我们使用高盐饮食诱导的高血压大鼠作为研究对象,分析了其组织(肾脏和结肠)和肠道微生物组的转录组,对肠道-肾脏轴进行了全面分析。我们旨在证实高盐和 1,25-二羟维生素 D3(calcitriol)对肠道-肾脏免疫系统和肠道菌群组成的影响。我们证明,高盐饮食会导致结肠和肾脏的高血压和炎症,以及肠道微生物群组成和功能的改变。高盐饮食诱导的高血压与 7 个微生物类群有关,主要与保护性短链脂肪酸丁酸的产生减少有关。1,25-二羟维生素 D3 可减轻结肠和肾脏炎症,并存在与恢复肠道屏障功能一致的基因表达变化。1,25-二羟维生素 D3 的保护作用可能通过免疫特性间接介导。此外,肠道微生物群介导的血压调节的分子途径可能与昼夜节律信号有关,这需要进一步研究。对微生物组进行创新性的关联分析可能是理解基因模式与宿主之间关联的关键策略。

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