基于调节肠道菌群失衡的四君子汤干预心力衰竭大鼠机制研究  

Mechanism Study of Sijunzi Decoction on Rats with Heart Failure Through Regulating the Imbalance of Intestinal Flora

作　　者：卢永康 陈窕圆[2] 庄贤勉 李健[2] 姜小艳 徐思思 黄彦子 黄彬[2] LU Yongkang;CHEN Tiaoyuan;ZHUANG Xianmian;LI Jian;JIANG Xiaoyan;XU Sisi;HUANG Yanzi;HUANG Bin(Shenzhen Hospital of Fuwai Hospital,Chinese Academy of Medical Sciences,Shenzhen 518000,China;Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518000,China)

机构地区：[1]中国医学科学院阜外医院深圳医院,广东深圳518000 [2]深圳市中医院,广东深圳518000

出　　处：《中国中医药信息杂志》2021年第4期81-87,共7页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：深圳市科技计划项目(JCYJ20170307155824718)。

摘　　要：目的从调节肠道菌群角度探讨四君子汤对心力衰竭大鼠的作用机制。方法40只雄性Wistar大鼠分为假手术组、模型组、四君子汤组及益生菌组,每组10只。采用冠状动脉左前降支结扎法制备心力衰竭大鼠模型,心电图及TTC、HE染色确定心肌梗死情况,HE染色检测肠黏膜结构变化,治疗前后超声评估心功能,并于治疗后行高通量测序检测肠道菌群的变化。结果心肌HE染色显示,模型组心肌细胞较假手术组数量减少,细胞形态萎缩,肌纤维疏松;结肠HE染色显示,模型组大鼠肠黏膜结构破坏,细胞排列紊乱,绒毛萎缩、粘连,隐窝减少、排列不规则,腺体正常结构消失、呈空泡状。超声结果显示,治疗前与假手术组比较,模型组大鼠心肌明显变薄,心腔增大,左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVESd)显著增加,左心室射血分数(LVEF)显著减少(P<0.001);治疗后与模型组比较,四君子汤组大鼠LVEDd、LVESd显著减少(P<0.001),LVEF显著增加(P<0.001)。测序结果显示,与假手术组比较,模型组大鼠出现肠道菌群失衡:在门分类水平,表现为厚壁菌门丰度显著减少(P<0.001),拟杆菌门及疣微菌门丰度显著增加(P<0.001,P<0.05);在属分类水平,表现为乳杆菌属、厌氧芽孢杆菌属丰度显著减少(P<0.001,P<0.05),Muribaculaceae_norank菌属、艾克曼菌属丰度显著增加(P<0.001,P<0.05)。与模型组比较,四君子汤组大鼠肠道菌群失衡显著改善:在门分类水平,厚壁菌门丰度显著增加,拟杆菌门丰度显著减少(P<0.05);在属分类水平,乳杆菌属、厌氧芽孢杆菌属丰度显著增加,Muribaculaceae_norank菌属丰度显著减少(P<0.05)。结论四君子汤通过调节肠道菌群失衡,对大鼠心肌梗死后心力衰竭有一定的治疗作用。Objective To explore the mechanism of Sijunzi Decoction on rat model with heart failure from the perspective of regulating intestinal flora.Methods Totally 40 male Wistar rats were divided into sham group,model group,Sijunzi Decoction group and probiotics group.Heart failure model was prepared by myocardial infarction induced by ligation of left anterior descending coronary artery,and myocardial infarction was confirmed by ECG,myocardium TTC and HE staining.Colon HE staining was performed for evaluation of intestinal mucosa structure under heart failure.Echocardiography was performed to evaluate cardiac function before and after treatment.The bacterial 16S rRNA sequencing was executed to detect intestinal flora.Results Myocardium HE staining showed that amount of cardiomyocytes of model group was less than that of the sham group,cell morphologic changes was atrophied,and myofiber was loose.Colon HE staining showed that damaged intestinal mucosal structure of the model group,disordered cell arrangement,atrophied and adhesive villi,irregularly arranged and reduced intestinal crypts,as well as the normal structure of the glands disappeared and becamed vacuolated.Echocardiography showed that myocardium of model group was significantly thinner than that of sham group before treatment,and heart chambers were enlarged,LVEDd and LVESd significantly increased,LVEF was significantly reduced(P<0.001);after treatment,compared with model group,LVEDd and LVESd were markedly reduced(P<0.001),as well as LVEF was markedly increased(P<0.001)in Sijunzi Decoction group.The sequencing results showed that compared with sham group,imbalance of intestinal flora was observed in model group:at the phylum level,the abundance of Firmicutes was significantly reduced(P<0.001),while the abundance of Bacteroidetes and Verrucomicrobia were significantly increased(P<0.001,P<0.05);at the genus level,the abundance of Lactobacillus and Clostridium sensu stricto 1 was significantly reduced(P<0.001,P<0.05),while the abundance of Muribaculaceae_norank

关 键 词：心力衰竭 肠道菌群 四君子汤 中药 大鼠 

分 类 号：R285.5[医药卫生—中药学]