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

作　　者：陈枝凡 陈钰璘 聂莎[1,2] 孙文昊 李畅 马梓珊 胡凯 何莹莹 刘鹰 唐耀平 CHEN Zhifan;CHEN Yulin;NIE Sha;SUN Wenhao;LI Chang;MA Zishan;HU Kai;HE Yingying;LIU Ying;TANG Yaoping(Guangxi University of Traditional Chinese Medicine,Nanning 530200,China;Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine,Nanning 530011;Guangxi Key Laboratory of Translational Medicine of Integrated Traditional Chinese and Western Medicine with High Infectious Diseases,Nanning 530200)

机构地区：[1]广西中医药大学,南宁530200 [2]广西中医药大学附属瑞康医院,南宁530011 [3]广西高发传染病中西医结合转化医学重点实验室,南宁530200

出　　处：《中国比较医学杂志》2024年第7期10-19,共10页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(82160856,81774115)。

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),TMAO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。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 Proteobacter

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 

分 类 号：R-33[医药卫生]