中国比较医学杂志2024,Vol.34Issue(7) :10-19.DOI:10.3969/j.issn.1671-7856.2024.07.002

瓜蒌薤白白酒汤调节肠道菌群及其代谢物改善小鼠动脉粥样硬化的实验研究

Mechanism of Gualou Xiebai Baijiu Decoction for regulating the intestinal microflora and its metabolites to improve atherosclerosis in mice

陈枝凡 陈钰璘 聂莎 孙文昊 李畅 马梓珊 胡凯 何莹莹 刘鹰 唐耀平
中国比较医学杂志2024,Vol.34Issue(7) :10-19.DOI:10.3969/j.issn.1671-7856.2024.07.002

瓜蒌薤白白酒汤调节肠道菌群及其代谢物改善小鼠动脉粥样硬化的实验研究

Mechanism of Gualou Xiebai Baijiu Decoction for regulating the intestinal microflora and its metabolites to improve atherosclerosis in mice

陈枝凡 1陈钰璘 1聂莎 1孙文昊 1李畅 1马梓珊 1胡凯 1何莹莹 1刘鹰 2唐耀平3
扫码查看

作者信息

  • 1. 广西中医药大学,南宁 530200;广西中医药大学附属瑞康医院,南宁 530011
  • 2. 广西中医药大学,南宁 530200
  • 3. 广西中医药大学,南宁 530200;广西中医药大学附属瑞康医院,南宁 530011;广西高发传染病中西医结合转化医学重点实验室,南宁 530200
  • 折叠

摘要

目的 探索瓜蒌薤白白酒汤通过调节肠道菌群(gut microbiota,GM)及其代产物从而改善小鼠动脉粥样硬化(atherosclerosis,AS)的作用机制.方法 将32只雄性ApoE-/-小鼠随机分为空白(Blank)组、模型(Model)组、阿托伐他汀(Ato)组、瓜蒌薤白白酒汤(GXB)组,每组8只.除Blank组以外的3组小鼠建立AS模型后按组别灌胃给药.用油红O染色检测主动脉斑块面积,HE染色观察主动脉组织病理变化.采用16S rRNA基因测序技术分析小鼠GM.检测小鼠GM代谢物氧化三甲胺(TMAO)、短链脂肪酸(SCFA)以及血清中TG、TC、LDL-C、HDL-C和NO水平.结果 与Blank组比较,Model组、Ato组AS斑块面积均增多(P<0.01、P<0.001);Model组血清TG、TC、LDL-C水平升高(P<0.001),HDL-C、NO水平降低(P<0.01、P<0.001).与Model组比较,Ato组、GXB组斑块面积减少(P<0.001);Ato组、GXB组中血清TG、TC、LDL-C水平降低(P<0.001),NO水平升高(P<0.01);GXB组HDL-C水平升高(P<0.05).与Ato组比较,GXB组斑块面积减少(P<0.05),NO水平升高(P<0.01).16S rRNA所得特征序列有6345个.α多样性分析提示GXB能降低AS小鼠GM的丰富度(P<0.001)并提升其均匀度(P<0.05).β多样性分析提示GXB组的菌群群落结构与Blank组较为相似.各组菌群丰度在门水平、属水平上均存在差异.门水平上,小鼠AS造模后Proteobacteria的丰度上升(P<0.01),GXB干预后能使其丰度下降(P<0.01)的同时提升Verrucomicrobiota的丰度(P<0.05).属水平上,GXB干预后能有效提升Akkermansia的丰度水平(P<0.05).与Model组比较,GXB组中SCFA水平显著升高(P<0.01),TMA O水平显著降低(P<0.01).结论 本研究发现,瓜蒌薤白白酒汤可以调节GM及其代谢物SCFA、TMAO来改善AS,Akkermansia可能是GXB通过GM改善AS的关键菌属.

Abstract

Objective To explore the mechanism of Gualou Xiebai Baijiu Decoction(GXB)in improving atherosclerosis(AS)in mice by regulating the gut microbiota(GM)and its metabolites.Methods Thirty-two male ApoE-/-mice were divided randomly into a Blank group,Model group,atorvastatin(Ato)group,and GXB group(n=8 mice per group).AS was established in all mice,except the Blank group,and the respective treatments were administered by gavage.Aortic plaques were detected by Oil red O staining and pathological changes in aortic tissue were detected by hematoxylin and eosin staining.The GM was analyzed using 16S rRNA gene sequencing technology,and mouse GM metabolites,including trimethylamine oxide(TMAO),short-chain fatty acids(SCFA),and serum levels of triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and nitric oxide(NO)were determined.Results Compared with the Blank group,mice in the Model and Ato groups showed an increase in AS plaque area(P<0.05).Serum levels of TG,TC,and LDL-C were increased(P<0.001)while levels of HDL-C and NO were decreased(P<0.01,P<0.001)in the Model group compared with the Blank group.The plaque area was decreased(P<0.05),serum levels of TG,TC,and LDL-C were decreased(P<0.001),and NO levels were increased(P<0.01)in the Ato and GXB groups,while HDL-C levels were increased in the GXB group(P<0.05)compared with the Model group.Plaque area was decreased(P<0.05)and the NO level was increased(P<0.01)in the GXB group compared with the Ato group.A total of 6345 characteristic sequences were obtained from 16S rRNA analysis.α-Diversity analysis indicated that GXB reduced the richness of the GM in AS mice(P<0.001)and improved its uniformity(P<0.05).β-Diversity analysis suggested that the microbial community structure in the GXB group was similar to that in the Blank group.The abundance of microbial communities differed among the groups at the phylum and genus levels.At the phylum level,the abundance of Proteobacteria was increased(P<0.01)in AS mice,while GXB intervention reduced the abundance of Proteobacteria(P<0.01)and increased the abundance of Verrucomimicrobiota(P<0.05).At the genus level,GXB effectively increased the abundance of Akkermansia(P<0.05).SCFAs were significantly increased(P<0.01)and TMAO levels were significantly decreased(P<0.01)in the GXB group compared with the Model group.Conclusions GXB can regulate the intestinal flora and intestinal flora metabolites SCFA and TMAO to improve AS.Akkermansia may be a key bacterial genus of the gut microbiota through which GXB may improve AS.

关键词

动脉粥样硬化/Akkermansia/16S/rRNA测序/瓜蒌薤白白酒汤/肠道菌群/肠道菌群代谢物

Key words

atherosclerosis/Akkermansia/16S rRNA sequencing/Gualou Xiebai Baijiu Decoction/gut microbiota/metabolites of gut microbiota

引用本文复制引用

基金项目

国家自然科学基金(82160856)

国家自然科学基金(81774115)

出版年

2024
中国比较医学杂志
中国实验动物学会,中国医学科学院医学实验动物研究所

中国比较医学杂志

CSTPCD北大核心
影响因子:0.473
ISSN:1671-7856
段落导航相关论文