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瑞士乳杆菌 R0052 和长双歧杆菌 R0175 的益生菌混合物可减轻脂多糖诱导的大鼠海马细胞凋亡。

Probiotic mixture of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 attenuates hippocampal apoptosis induced by lipopolysaccharide in rats.

机构信息

Cellular and Molecular Research Center, Department of Molecular Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Int Microbiol. 2019 Sep;22(3):317-323. doi: 10.1007/s10123-018-00051-3. Epub 2018 Dec 11.

DOI:10.1007/s10123-018-00051-3
PMID:30810993
Abstract

In recent years, the beneficial impact of targeted gut microbiota manipulation in various neurological disorders has become more evident. Therefore, probiotics have been considered as a promising approach to modulate brain gene expression and neuronal pathways even in some neurodegenerative diseases. The purpose of this study was to determine the effect of probiotic biotherapy with combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on the expression levels of proteins critical to neuronal apoptosis in hippocampus of lipopolysaccharide (LPS)-exposed rats. Four groups of animals (Control, LPS, Probiotic + LPS, and Probiotic) were treated with maltodextrin (placebo) or probiotic (10 CFU/ml/rat) for 2 weeks by gavage. On the 15th day, a single intraperitoneal dose of saline or LPS (1 mg/kg) was injected and 4 h later, protein assessment was performed by western blotting in hippocampal tissues. LPS significantly increased the Bax, Bax/Bcl-2 ratio, and cleaved caspase-3 expression along with decreased the Bcl-2 and procaspase-3 protein levels. However, probiotic pretreatment (L. helveticus R0052 + B. longum R0175) significantly downregulated the Bax and Bax/Bcl-2 ratio accompanied with upregulated Bcl-2 expression. Prophylactic treatment with these bacteria also attenuated LPS-induced caspase-3 activation by remarkably increasing the expression of procaspase-3 while reducing the level of cleaved caspase-3 in target tissues. Our data indicate that probiotic formulation (L. helveticus R0052 + B. longum R0175) alleviated hippocampal apoptosis induced by LPS in rats via the gut-brain axis and suggest that this probiotic could play a beneficial role in some neurodegenerative conditions.

摘要

近年来,靶向肠道微生物群操纵在各种神经障碍中的有益影响变得更加明显。因此,益生菌已被认为是一种有前途的方法,可以调节大脑基因表达和神经元途径,即使在一些神经退行性疾病中也是如此。本研究的目的是确定含有瑞士乳杆菌 R0052 和长双歧杆菌 R0175 的益生菌生物疗法对脂多糖 (LPS) 暴露大鼠海马中与神经元凋亡相关的关键蛋白表达水平的影响。将四组动物(对照组、LPS 组、益生菌+LPS 组和益生菌组)分别用麦芽糖糊精(安慰剂)或益生菌(10 CFU/ml/大鼠)通过灌胃处理 2 周。在第 15 天,大鼠腹腔内单次注射生理盐水或 LPS(1mg/kg),4 小时后,通过 Western blot 法评估海马组织中的蛋白质。LPS 显著增加了 Bax、Bax/Bcl-2 比值和 cleaved caspase-3 的表达,同时降低了 Bcl-2 和 procaspase-3 的蛋白水平。然而,益生菌预处理(瑞士乳杆菌 R0052+B. longum R0175)显著下调了 Bax 和 Bax/Bcl-2 比值,同时上调了 Bcl-2 的表达。这些细菌的预防性治疗还通过显著增加 procaspase-3 的表达并降低靶组织中 cleaved caspase-3 的水平来减弱 LPS 诱导的 caspase-3 激活。我们的数据表明,益生菌配方(瑞士乳杆菌 R0052+B. longum R0175)通过肠道-大脑轴减轻了 LPS 诱导的大鼠海马细胞凋亡,并表明这种益生菌可能在一些神经退行性疾病中发挥有益作用。

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