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实验性牙周病引发中年大鼠冠状动脉内皮功能障碍:一种益生菌 β-葡聚糖的预防作用。

Experimental Periodontal Disease Triggers Coronary Endothelial Dysfunction in Middle-Aged Rats: Preventive Effect of a Prebiotic β-Glucan.

机构信息

Faculty of Health, Centro Universitário de Lavras (UNILAVRAS), Lavras, Minas Gerais, Brazil.

Department of Health Sciences, Universidade Federal de Lavras (UFLA), Lavras, Minas Gerais, Brazil.

出版信息

J Gerontol A Biol Sci Med Sci. 2021 Jul 13;76(8):1398-1406. doi: 10.1093/gerona/glab066.

Abstract

This study was aimed to verify the hypothesis that periodontal disease contributes to endothelial dysfunction in the coronary arteries of middle-aged rats. Besides we evaluated the effects of a prebiotic (β-glucan isolated from Saccharomyces cerevisiae) in preventing vascular dysfunction. The sample comprised young (sham and induced to periodontal disease) and middle-aged rats (sham, periodontal disease, sham-treated and periodontal disease-treated), at 12 and 57 weeks, respectively. The treated-groups received daily doses of β-glucan (50 mg/kg) orally (gavage) for 4 weeks, and periodontal disease was induced in the last 2 weeks by ligature. A myograph system assessed vascular reactivity. The expression of endothelial nitric oxide synthase (eNOS), cyclooxygenase 1 (COX-1), COX-2, p47phox, gp91phox, NF-KB p65, p53, p21, and p16 was quantified by western blotting. Serum hydroperoxide production was measured by the ferrous oxidation-xylenol orange (FOX-2) assay method. Interleukin-1 beta (IL-1β), IL-10, and tumor necrosis factor-alpha (TNF-α) levels were evaluated by spectroscopic ultraviolet-visible analysis. Periodontal disease in middle-aged rats was associated with reduced acetylcholine-induced relaxations of coronary artery rings affecting the endothelium-dependent hyperpolarization- and the nitric oxide-mediated relaxations. The endothelial dysfunction was related to eNOS downregulation, pronounced impairment of the EDH-mediated relaxation, increased IL-1β and TNF-α proinflammatory cytokines, and also upregulation of NADPH oxidase and COXs, starting accumulate aging markers such as p53/p21 and the p16. Treatment with β-glucan effectively reduced bone loss in periodontal disease and delayed endothelial dysfunction in the coronary artery. Our data show that yeast β-glucan ingestion prevented oxidative stress and synthesis of proinflammatory marker and prevented eNOS reduction induced by periodontal disease in middle-aged rats. These results suggest that β-glucan has a beneficial effect on the coronary vascular bed.

摘要

本研究旨在验证牙周病导致中年大鼠冠状动脉内皮功能障碍的假说。此外,我们还评估了一种益生元(来自酿酒酵母的β-葡聚糖)在预防血管功能障碍方面的作用。样本包括年轻(假手术和诱导牙周病)和中年(假手术、牙周病、假手术治疗和牙周病治疗)大鼠,分别在 12 周和 57 周时。治疗组每天口服β-葡聚糖(50mg/kg)(灌胃)4 周,在最后 2 周通过结扎诱导牙周病。血管反应性通过肌动描记系统进行评估。通过 Western blot 定量检测内皮型一氧化氮合酶(eNOS)、环氧化酶 1(COX-1)、COX-2、p47phox、gp91phox、NF-KB p65、p53、p21 和 p16 的表达。通过亚铁氧化-二甲氧苯酚橙(FOX-2)法测定血清羟自由基生成。通过分光光度紫外可见分析评估白细胞介素-1β(IL-1β)、IL-10 和肿瘤坏死因子-α(TNF-α)水平。中年大鼠牙周病与冠状动脉环乙酰胆碱诱导松弛减少有关,影响内皮依赖性超极化和一氧化氮介导的松弛。内皮功能障碍与 eNOS 下调有关,显著损害 EDH 介导的松弛,增加促炎细胞因子 IL-1β 和 TNF-α,以及 NADPH 氧化酶和 COXs 的上调,开始积累衰老标志物如 p53/p21 和 p16。β-葡聚糖治疗可有效减少牙周病的骨质流失,并延迟中年大鼠冠状动脉内皮功能障碍。我们的数据表明,酵母β-葡聚糖摄入可防止牙周病引起的氧化应激和促炎标志物合成,并防止 eNOS 减少。这些结果表明,β-葡聚糖对冠状动脉血管床具有有益作用。

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