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纳豆摄入可抑制 LDL 受体缺陷型小鼠移植表达 iRFP 造血细胞后的动脉粥样硬化斑块进展。

Natto consumption suppresses atherosclerotic plaque progression in LDL receptor-deficient mice transplanted with iRFP-expressing hematopoietic cells.

机构信息

Tsukuba Medical Center Hospital, 1-3-1, Amakubo, Tsukuba, Ibaraki, 305-8558, Japan.

Doctoral Program in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

出版信息

Sci Rep. 2023 Dec 18;13(1):22469. doi: 10.1038/s41598-023-48562-y.

DOI:10.1038/s41598-023-48562-y
PMID:38110459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10728071/
Abstract

Natto, known for its high vitamin K content, has been demonstrated to suppress atherosclerosis in large-scale clinical trials through a yet-unknown mechanism. In this study, we used a previously reported mouse model, transplanting the bone marrow of mice expressing infra-red fluorescent protein (iRFP) into LDLR-deficient mice, allowing unique and non-invasive observation of foam cells expressing iRFP in atherosclerotic lesions. Using 3 natto strains, we meticulously examined the effects of varying vitamin K levels on atherosclerosis in these mice. Notably, high vitamin K natto significantly reduced aortic staining and iRFP fluorescence, indicative of decreased atherosclerosis. Furthermore, mice administered natto showed changes in gut microbiota, including an increase in natto bacteria within the cecum, and a significant reduction in serum CCL2 expression. In experiments with LPS-stimulated macrophages, adding natto decreased CCL2 expression and increased anti-inflammatory cytokine IL-10 expression. This suggests that natto inhibits atherosclerosis through suppression of intestinal inflammation and reduced CCL2 expression in macrophages.

摘要

纳豆因其高维生素 K 含量而闻名,通过一种未知的机制,在大规模临床试验中已被证明可以抑制动脉粥样硬化。在这项研究中,我们使用了之前报道的一种小鼠模型,将表达近红外荧光蛋白(iRFP)的小鼠的骨髓移植到 LDLR 缺陷型小鼠中,从而可以对动脉粥样硬化病变中表达 iRFP 的泡沫细胞进行独特的、非侵入性的观察。我们使用了 3 株纳豆,细致地研究了不同维生素 K 水平对这些小鼠动脉粥样硬化的影响。值得注意的是,高维生素 K 纳豆显著减少了主动脉的染色和 iRFP 荧光,表明动脉粥样硬化减少。此外,给予纳豆的小鼠的肠道微生物群发生了变化,包括盲肠内纳豆细菌的增加,以及血清 CCL2 表达的显著减少。在 LPS 刺激的巨噬细胞实验中,添加纳豆可降低 CCL2 的表达并增加抗炎细胞因子 IL-10 的表达。这表明纳豆通过抑制肠道炎症和减少巨噬细胞中 CCL2 的表达来抑制动脉粥样硬化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdb/10728071/c1a7103ea84c/41598_2023_48562_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdb/10728071/eaaec0d84ced/41598_2023_48562_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdb/10728071/81bf178a4b99/41598_2023_48562_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdb/10728071/d5219e376a93/41598_2023_48562_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdb/10728071/c1a7103ea84c/41598_2023_48562_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdb/10728071/eaaec0d84ced/41598_2023_48562_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdb/10728071/81bf178a4b99/41598_2023_48562_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdb/10728071/d5219e376a93/41598_2023_48562_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdb/10728071/c1a7103ea84c/41598_2023_48562_Fig4_HTML.jpg

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