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白藜芦醇对动脉粥样硬化模型大鼠氧化三甲胺及肠道菌群的调控作用研究
王玉涛,杨丽科,王华雨,孙岩
山东中医药大学第一临床医学院济南 250012;中国中医科学院广安门医院济南医院济南市中医医院周围血管病科济南 250014;山东第一医科大学附属省立医院血管外科济南 250021
摘要:
目的:探讨白藜芦醇(RES)对动脉粥样硬化(AS)大鼠的血脂水平、氧化三甲胺(TMAO)、炎症因子和肠道菌群丰度的调控作用。方法:将24只大鼠随机均分为对照组、AS组和RES组,AS组和RES组大鼠采用腹主动脉球囊损伤法联合高脂饲料喂养2周复制AS模型。造模次日开始灌胃给药,1次/d,连续4周。采用主动脉苏木精-伊红(HE)染色、血脂水平验证RES干预AS的效果,检测各组大鼠TMAO、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的表达水平,使用宏基因组测序分析肠道内容物肠道菌群丰度。结果:与对照组比较,AS组大鼠血清三酰甘油(TG)、总胆固醇(TC)、TNF-α、IL-6和TMAO水平升高;肠道菌群生物多样性减少;在门水平上,厚壁菌门和放线菌门相对丰度下调,拟杆菌门和尾噬菌体门相对丰度上调;在纲水平上,放线菌纲、芽孢杆菌纲和梭菌纲相对丰度下调,拟杆菌纲、丹毒丝菌纲和γ变形菌纲相对丰度上调;在属水平上,拟杆菌属、埃希菌属、鼠肠杆菌属和副拟杆菌属相对丰度上调,双歧杆菌属、乳杆菌属、唾液乳杆菌属、罗伊氏乳杆菌属、甲烷球形菌属和罗氏菌属相对丰度下调。与AS组比较,RES组大鼠血清TC、TNF-α、IL-6和TMAO水平降低;RES上调了AS大鼠肠道菌群生物多样性和厚壁菌门、芽孢杆菌纲、梭菌纲、双歧杆菌属、乳杆菌属、唾液乳杆菌属、罗伊氏乳杆菌属和罗氏菌属的相对丰度,下调了尾噬菌体门、拟杆菌门、拟杆菌纲、丹毒丝菌纲、γ变形菌纲、拟杆菌属、埃希菌属和鼠肠杆菌属的相对丰度,差异均有统计学意义(P <0.05)。结论:RES可调节AS大鼠的血脂水平,降低TNF-α、IL-6和TMAO的表达水平,上调有益菌群的丰度,下调有害菌群的丰度,从而调节肠道菌群的多样性。
关键词:  白藜芦醇  动脉粥样硬化  氧化三甲胺肠道菌群
DOI:10.3969/j.issn.1007-6948.2025.03.017
投稿时间:2024-11-02
基金项目:国家自然科学基金青年基金项目(82104860);山东省自然科学基金(ZR2022MH268);山东省中医药科技发展计划(2019-0559);济南市卫生健康委员会科技计划项目(2019-1-23);山东省医药卫生科技发展计划(2018WS273、2018WS478);济南市临床医学科技创新计划(202134013)
Study on the regulatory effects of resveratrol on trimethylamine N-oxide level and intestinal flora abundance in atherosclerosis model rats
WANG Yu-tao,YANG Li-ke,WANG Hua-yu
Abstract:
Objective To investigate the regulatory effects of resveratrol (RES) on trimethylamine N-oxide (TMAO) level and intestinal flora abundance in atherosclerosis (AS) rats. Methods Twenty-four rats were randomly divided into control group, AS group and RES intervention group. Rats in the AS group and RES intervention group were fed with abdominal aortic balloon injury method combined with high-fat chow for 2 weeks to replicate the AS model. The drug was administered by gavage starting on the next day of modeling, once daily for 4 weeks. Aortic hematoxylin-eosin (HE) staining and lipid levels were used to verify the effect of RES intervention in AS, and the abundance of intestinal flora in intestinal contents was analyzed using metagenomics. Results Compared with the control group, serum triglyceride (TG), total cholesterol (TC), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and TMAO level of AS group rats were elevated. The intestinal bacterial biodiversity was reduced. At the level of the phylum, the relative abundance of Firmicutes and the Actinobacteria were down-regulated, and the relative abundance of Bacteroidetes and Uroviricota was up-regulated. At the class level, the relative abundance of Actinomycetia, Bacilli and Clostridia was down-regulated, the relative abundance of Bacteroidia, Erysipelotrichia and Gammaproteobacteria was up-regulated. At the genus level, the relative abundance of Bacteroides, Escherichia, Muribaculum, and Parabacteroides was up-regulated, and the relative abundance of Bifidobacterium, Lactobacillus, Ligilactobacillus, Limosilactobacillus, Methanosphaera and Romboutsia was down-regulated. In comparison to the AS group, the serum TC, TNF-α, IL-6 and TMAO of rats in RES intervention group were decreased. RES up-regulated the biodiversity of intestinal flora and the relative abundance of Firmicutes, Bacilli, Clostridia, Bifidobacterium, Lactobacillus, Ligilactobacillus, Limosilactobacillus, and Romboutsia in AS model rats, and down-regulated the relative abundance of Uroviricota, Bacteroidetes, Bacteroidia, Erysipelotrichia, Gammaproteobacteria and Muribaculum, with all differences were statistically significant (P <0.05). Conclusion RES can regulate lipid levels in AS rats, reduce the expression of TNF-α, IL-6, and TMAO, upregulate the abundance of beneficial microbiota, downregulate the abundance of harmful microbiota, and modulate the diversity of the gut microbiota.
Key words:  Resveratrol  atherosclerosis  trimethylamine N-oxide intestinal flora

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