向日葵花盘通过调节肠道菌群改善ApoE^(-/-)小鼠动脉粥样硬化研究  

Helianthus Annuus L.alleviates atherosclerosis by modulating gut microbiota in ApoE^(-/-)mice

作　　者：王健兵[1] 阴丽 盛艳玲[2] 单士军 Wang Jianbing;Yin Li;Sheng Yanling;Shan Shijun(Cardiovascular Medicine Department,General Hospital of Huabei Petroleum Administration Bureau,Renqiu,Hebei 062552,China;Department of Respiratory and Critical Care Medicine,General Hospital of Huabei Petroleum Administration Bureau,Renqiu,Hebei 062552,China;Internal Medicine Department,North China Petroleum Hospital of Traditional Chinese Medicine,Renqiu,Hebei 062552,China;Dermatology Department,Hangzhou Third People's Hospital,Affiliated Hangzhou Dermatology Hospital,School of Medicine,Zhejiang University,Hangzhou 310000,China)

机构地区：[1]华北石油管理局总医院心血管内科,河北任丘062552 [2]华北石油管理局总医院呼吸与危重症学科,河北任丘062552 [3]华北石油管理局中医医院内科,河北任丘062552 [4]杭州市第三人民医院、浙江大学医学院附属杭州市皮肤病医院皮肤科,浙江杭州310000

出　　处：《兰州大学学报（医学版）》2023年第7期16-26,共11页Journal of Lanzhou University（Medical Sciences）

基　　金：河北省卫健委重点科技研究计划资助项目(20210857)。

摘　　要：目的探讨向日葵花盘(HAL)对高脂饮食诱导的动脉粥样硬化(AS)的药效作用,并通过观察肠道菌群、肠道通透性及炎症因子变化阐明其相关作用机制。方法缺乏载脂蛋白E(Apo E^(-/-))的小鼠随机分为3组:对照组给予普通饲料,模型组(AS)给予高脂饲料(HFD),HAL组给予喂食混合5%HAL的HFD。24周后,对3组小鼠血脂和主动脉斑块情况进行分析比较,观察HAL对AS的改善作用并探讨其机制。结果与AS组比较,HAL干预改善了高脂饮食诱导的血脂异常和主动脉动脉粥样硬化病变(P<0.05)。HAL干预下调了小鼠肠道厚壁菌门与拟杆菌门的比值,上调了嗜黏蛋白阿克曼菌和乳酸菌的相对丰度,并下调了未分类的肠杆菌、鞘氨醇单胞菌和甲基杆菌的相对丰度(P<0.05)。HAL干预上调了小鼠结肠中闭合蛋白的水平(P<0.05),降低肠道通透性,从而减少炎症物质入血,降低了小鼠白介素-6(IL-6),IL-1β和肿瘤坏死因子-α的浓度及主动脉mRNA表达(P<0.05),降低了主动脉核因子κB(NF-κB)和诱导型一氧化氮合酶(iNOS)表达(P<0.01)。结论HAL可改善HFD诱导的主动脉粥样硬化病变,其作用机制为调节肠道菌群、降低肠壁通透性和抑制NF-κB和iNOS表达。Objective To confirm the effect of Helianthus Annuus L.(HAL)on high-fat diet-induced atherosclerosis(AS),and to elucidate related mechanisms by observing the changes in intestinal flora,intestinal permeability and inflammatory factors.Methods In our study,mice lacking apolipoprotein E(APOE^(-/-))were randomly divided into 3 groups.The control group was fed with a normal diet,while AS group with a high-fat diet(HFD)and HAL group with HFD mixed with 5%HAL.After 24 weeks,the blood lipids and aortic plaques of mice in three groups were analyzed and compared,the ameliorative effect of HAL on AS observed and then the possible mechanisms explored.Results Compared with the AS group,HAL treatment improved the blood lipid abnormalities induced by HFD and reduced the degree of aortic AS(P<0.05).HAL treatment down-regulated the ratio of Firmicutes to Bacteroidetes in mouse intestines,up-regulated the relative abundance of Akkermansia muciniphila,Lactobacillus,and down-regulated the relative abundance of unidentified Enterobateriaceae,Sphingomonas,and Methylobacterium(P<0.05).In addition,HAL treatment up-regulated the levels of occludin in the colon of mice(P<0.05),decreased intestinal permeability and thus reduced the influx of inflammatory substances into the bloodstream;as a result,the concentration of interleukin(IL)-6,IL-1β,tumor necrosis factor-αand their mRNA expression in the aorta were decreased(P<0.05).In the end,the expression of nuclear factorκB(NF-κB)and inducible nitric oxide synthase(iNOS)in the aorta was decreased(P<0.01).Conclusion Our data showed that HAL treatment alleviated AS induced by HFD by modulating gut microbiota,thus reducing intestinal permeability and inhibiting the expression of NF-κB and iNOS.

关 键 词：向日葵花盘 动脉粥样硬化 肠道菌群 闭合蛋白 肠壁通透性 炎症因子 

分 类 号：R54[医药卫生—心血管疾病]