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植物乳杆菌 ATCC 14917 通过调节促炎细胞因子和氧化应激对载脂蛋白 E 基因敲除小鼠的抗动脉粥样硬化作用。

Anti-atherosclerotic effects of Lactobacillus plantarum ATCC 14917 in ApoE mice through modulation of proinflammatory cytokines and oxidative stress.

机构信息

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.

Drug Discovery Research Centre, Southwest Medical University, Luzhou, 646000, China.

出版信息

Appl Microbiol Biotechnol. 2020 Jul;104(14):6337-6350. doi: 10.1007/s00253-020-10693-x. Epub 2020 May 29.

Abstract

Atherosclerosis is a chronic inflammatory disease mediated by monocyte infiltration and cholesterol deposition into the subendothelial area, resulting in foam cell development. Probiotics are live bacteria that are beneficial for health when administered orally in adequate amounts. In this study, 8-week-old atherosclerosis-prone apolipoprotein E-deficient (ApoE) mice were fed with or without Lactobacillus plantarum ATCC 14917 per day for 12 weeks. Serum was collected to analyse the lipid profile, oxidative status and proinflammatory cytokines. The heart was isolated to quantify the atherosclerotic lesion size in the aortic arch. Quantitative real-time polymerase chain reaction was performed to determine the expression levels of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in the aorta. The proteins extracted from the aorta were used for Western blot analysis to assess the expression levels of nuclear factor kappa B (NF-κB) and inhibitor of NF-κB (IκBα). The composition of gut microbiota was also examined through high-throughput sequencing. Results showed that the daily consumption of L. plantarum ATCC 14917 had no effect on body weight and lipid profile. L. plantarum ATCC 14917 treatment significantly inhibited atherosclerotic lesion formation. In addition, the oxLDL, MDA, TNF-α and IL-1β levels were significantly reduced, whereas the SOD level was induced in the bacteria + high-fat diet group. Furthermore, the administration of L. plantarum ATCC 14917 significantly attenuated IκBα protein degradation and inhibited the translocation of P65 subunits of NF-κB. L. plantarum ATCC 14917 treatment also modulated the composition of gut microbiota in ApoE mice. Our findings showed that L. plantarum ATCC 14917 supplementation decreases the progression of atherosclerotic lesion formation by alleviating the inflammatory process and lowering oxidative stress.

摘要

动脉粥样硬化是一种慢性炎症性疾病,由单核细胞浸润和胆固醇沉积到血管内皮下区域引起,导致泡沫细胞的形成。益生菌是指当以足够的量口服给予时对健康有益的活细菌。在这项研究中,给 8 周龄的易患动脉粥样硬化的载脂蛋白 E 缺陷(ApoE)小鼠每天喂食或不喂食植物乳杆菌 ATCC 14917,持续 12 周。收集血清以分析血脂谱、氧化状态和促炎细胞因子。分离心脏以定量主动脉弓中的动脉粥样硬化病变大小。进行实时定量聚合酶链反应以确定主动脉中肿瘤坏死因子-α(TNF-α)和白细胞介素(IL)-1β的表达水平。从主动脉提取蛋白质,用于 Western blot 分析以评估核因子 kappa B(NF-κB)和 NF-κB 抑制剂(IκBα)的表达水平。还通过高通量测序检查肠道微生物组的组成。结果表明,每天食用植物乳杆菌 ATCC 14917 对体重和血脂谱没有影响。植物乳杆菌 ATCC 14917 处理显著抑制动脉粥样硬化病变的形成。此外,oxLDL、MDA、TNF-α和 IL-1β水平显著降低,而细菌+高脂饮食组的 SOD 水平升高。此外,给予植物乳杆菌 ATCC 14917 可显著减轻 IκBα 蛋白降解并抑制 NF-κB P65 亚基的易位。植物乳杆菌 ATCC 14917 处理还调节了 ApoE 小鼠肠道微生物组的组成。我们的研究结果表明,植物乳杆菌 ATCC 14917 的补充通过减轻炎症过程和降低氧化应激来减少动脉粥样硬化病变形成的进展。

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