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布拉氏酵母菌通过调节氧化应激、肾素-血管紧张素系统和尿路致病性微生物群在糖尿病小鼠模型中发挥肾保护作用。

Saccharomyces boulardii exerts renoprotection by modulating oxidative stress, renin angiotensin system and uropathogenic microbiota in a murine model of diabetes.

机构信息

Federal University of São Paulo (UNIFESP), Department of Medicine, São Paulo, SP, Brazil.

Medpace Core Laboratories - Lyon, Auvergne-Rhône-Alpes, France.

出版信息

Life Sci. 2022 Jul 15;301:120616. doi: 10.1016/j.lfs.2022.120616. Epub 2022 May 6.

Abstract

AIMS

We aimed to investigate whether Saccharomyces boulardii strain might exert renoprotective effects by modulating renal renin angiotensin system, oxidative stress and intestinal microbiota in streptozotocin-diabetic mice.

MAIN METHODS

Thirty-six C57BL/6 male mice were divided into four groups: control (C), control + probiotic (CP), diabetes (D), diabetes + probiotic (DP). Diabetes was induced by one intraperitoneal injection of streptozotocin and Saccharomyces boulardii was administered by oral gavage for 8 weeks. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7) and the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined, besides that, renal morphology, serotonin and dopamine levels and also microbiota composition were analyzed.

KEY FINDINGS

Probiotics significantly increased C-peptide secretion and reduced blood glucose of diabetic animals. Saccharomyces boulardii also improved renal antioxidant defense, restored serotonin and dopamine concentration, and activated the renin-angiotensin system (RAS) vasodilator and antifibrotic axis. The modulation of these markers was associated with a beneficial impact on glomerular structure and renal function of diabetic treated animals. The phenotypic changes induced by Saccharomyces boulardii were also related to modulation of intestinal microbiota, evidenced by the decreased abundance of Proteus and Escherichia-Shigella, considered diabetic nephropathy biomarkers.

SIGNIFICANCE

Therefore, probiotic administration to streptozotocin-induced diabetic mice improves kidney structure and function in a murine model and might represent a reasonable strategy to counteract nephropathy-associated maladaptive responses in diabetes.

摘要

目的

我们旨在研究酿酒酵母布拉氏酵母菌是否通过调节肾素-血管紧张素系统、氧化应激和肠道微生物群来发挥对糖尿病肾病的保护作用。

方法

36 只 C57BL/6 雄性小鼠分为四组:对照组(C)、对照组+益生菌(CP)、糖尿病组(D)、糖尿病+益生菌(DP)。通过单次腹腔注射链脲佐菌素诱导糖尿病,并用口服灌胃法给予酿酒酵母布拉氏酵母菌 8 周。测量血糖、蛋白尿和尿量。测定肾血管紧张素肽(血管紧张素 I、II 和 1-7)水平和血管紧张素转换酶(ACE)和 ACE2 的活性,此外还分析了肾脏形态、血清素和多巴胺水平以及微生物群组成。

主要发现

益生菌显著增加了糖尿病动物的 C 肽分泌并降低了血糖。酿酒酵母布拉氏酵母菌还改善了肾脏抗氧化防御,恢复了血清素和多巴胺浓度,并激活了肾素-血管紧张素系统(RAS)的血管舒张和抗纤维化轴。这些标志物的调节与改善糖尿病治疗动物的肾小球结构和肾功能有关。酿酒酵母布拉氏酵母菌引起的表型变化也与肠道微生物群的调节有关,这一点可以通过减少被认为是糖尿病肾病生物标志物的变形菌属和埃希氏-志贺氏菌属的丰度来证明。

意义

因此,给链脲佐菌素诱导的糖尿病小鼠施用益生菌可改善其肾脏结构和功能,这可能是一种对抗糖尿病相关适应性反应的合理策略。

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