Pathological Mechanism of “Phlegm, Blood stasis, Toxin ”in a Rabbit Model of Carotid Atherosclerosis Based on Gut Microbiota-host Metabolism Interactions  

作　　者：Feng Zhang Yanyun Xu Liye Shen Junjie Huang Songtao Xu Minli Chen Yongming Pan 

机构地区：[1]The Second School of Clinical Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China [2]Academy of Chinese Medical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China [3]School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 311402,Zhejiang,China [4]Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province,Hangzhou 310006,Zhejiang,China

出　　处：《Clinical Complementary Medicine and Pharmacology》2023年第2期10-21,共12页临床补充医学和药理学（英文）

基　　金：funded by the National Natural Science Founda-tion of China(No.31970514);Opening Project of Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treat-ment of Circulatory Diseases of Zhejiang Province(No.2C32102).

摘　　要：Background:In Traditional Chinese Medicine(TCM)theory,"phlegm,blood stasis and toxin"are the pathogenesis of carotid atherosclerosis(CAS).The rabbit carotid atherosclerosis(CAS),which is induced by high-cholesterol diet combined with carotid artery balloon injury,is a classic model for studying CAS.Many studies indicate that gut microbiota and host metabolic disorders are involved in the pathogenesis of rabbit CAS.However,the TCM pathological features and syndromes of this classic rabbit CAS model have not been reported.Objective:To explore the pathogenesis of the rabbit CAS model and its TCM syndrome types from the perspective of"phlegm,blood stasis,and toxin".Methods:Twelve male New Zealand white rabbits were randomly divided into NC group and CAS group according to their body weight,followed by feeding of basic feed and a 1%high cholesterol diet,respectively.After two weeks,the rabbits in the CAS group underwent common carotid artery(CCA)balloon injury,while the rabbits in the NC group underwent only CCA separation without balloon injury.The two groups received differential feed postoperatively for six more weeks,after which,changes in lipids,hemorheology,inflammation,oxidative stress,and CAS phenotypes were analyzed.In addition,the colon contents and serum were collected for 16S rRNA sequencing and ^(1)H-NMR metabonomic analysis.Results:The CAS rabbits were observed to form noticeable abnormalities in lipid metabolism and blood rhe-ology,a sharp increase in oxidative stress levels,excessive release of inflammatory factors and apparent CAS plaque formation.Furthermore,10 specific gut microbiota(such as Akkermansia muciniphila,Barnesiellaceae and Faecalibacterium)and 14 characteristic metabolites(such as trimethylamine oxide,acetic acid and L-carnitine)were identified in the CAS rabbits,which were significantly related to the CAS phenotypes.The pathway func-tion analysis showed that the gut microbiota and its metabolites mainly affected cholesterol metabolism,energy metabolism,inflammation and oxidative stress.

关 键 词：Carotid atherosclerosis PHLEGM Blood stasis TOXIN Gut microbiota Host metabolism Animal model 

分 类 号：R543.5[医药卫生—心血管疾病]