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慢性心理应激对高脂饮食ApoE^(-/-)小鼠肠道菌群的影响

Impact of chronic psychological stress on the gut microbiota of ApoE^(-/-) mice fed with high fat diet
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摘要 目的 探讨慢性心理应激(CPS)对小鼠动脉粥样硬化(AS)发生发展的影响及观察肠道菌群的变化。方法 10只雄性C57BL/6J小鼠设为正常对照(NC)组,予以普通饲料喂养;20只雄性ApoE^(-/-)小鼠均予以高脂饮食,随机分为AS组和AS+CPS组。AS+CPS组小鼠通过12周的慢性温和不可预见性应激(CUMS)方案构建CPS模型。检测血浆三酰甘油、总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇浓度,血管病理切片HE染色观察斑块形态。采集小鼠粪便扩增肠道菌群16S rRNA基因的V3+V4区,采用高通量测序检测小鼠肠道菌群组成,分析α和β多样性。结果 与NC组和AS组小鼠比较,AS+CPS组小鼠体重增长缓慢,旷场实验反应箱中心区域停留时间显著减少(P<0.05)。此外,AS+CPS组小鼠AS斑块面积显著增加(P<0.01),管腔狭窄严重(P<0.01)。AS组和AS+CP组小鼠肠道菌群多样性下降,肠道菌群物种组成也发生改变。结论 高脂饮食可导致小鼠AS形成及肠道菌群紊乱,有益菌丰度下降,有害菌丰度增加,且CPS可促进AS病变并加重肠道菌群紊乱。 Objective To investigate the effect of chronic psychological stress(CPS) on development of atherosclerosis and observe the changes of gut microbiota in ApoE^(-/-) mice fed with high fat diet.Methods 10 male C57 BL/6 J mice fed with the normal diet were set as normal control group(NC).20 male ApoE^(-/-) mice fed with high-fat diet were randomly divided into atherosclerotic group(AS group) and atherosclerotic+CPS group(AS+CPS group).The AS+CPS mice received chronic mild and unpredictable stress(CUMS) for 12 weeks.The concentration of plasma triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol were detected,and AS plaques of arterial sections were observed by method of HE staining.The gut microbiota was amplified targeting V3+V4 region of 16 S rRNA gene.The species composition was analyzed by high-throughput sequencing at phylum and genus level.Results Compare with NC group and AS group,the weight of mice in the AS+CPS group increased slowly,the residence time in the central area of the reaction box in the open field was markedly reduced,and CPS significantly increased plaque area(P<0.01) and aggravated lumen stenosis(P<0.01).The diversity of intestinal flora in AS group and AS+CPS group decreased,and the composition of gut microbiota was significantly different among the groups.Conclusions High fat diet can cause AS formation and intestinal microflora disorder in mice,and the relative abundance of beneficial gut microbiota decreases while the relative abundance of harmful gut microbiota increases.CPS may promote the development of AS and aggravate disorder of gut microbiota in mice.
作者 王立 孟令丙 徐鸿轩 陈玉辉 尹家文 王倩雯 刘德平 龚涛 Wang Li;Meng Lingbing;Xu Hongxuan;Chen Yuhui;Yin Jiawen;Wang Qianwen;Liu Deping;Gong Tao(The Key Laboratory of Geriatrics,Beijing Institute of Geriatrics,Institute of Geriatrics Medicine,Chinese Academy of Medical Science,Beijing Hospital,National Center of Gerontology of National Health Commission,Beijing 100730,China;Department of Neurology,Beijing Hospital,Beijing 100730,China;Departments of Cardiology,Beijing Hospital,Beijing 100730,China)
出处 《中国心血管杂志》 2022年第2期157-164,共8页 Chinese Journal of Cardiovascular Medicine
基金 国家重点研发计划项目(2020YFC2003000) 中国医学科学院医学科学创新基金项目(2018-I2M-1-002) 中央卫生科研计划项目(W2017BJ11)。
关键词 动脉粥样硬化 高脂饮食 肠道菌群 慢性心理应激 Atherosclerosis High fat diet Gut microbiota Chronic psychological stress
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