通冠胶囊对急性ST段抬高型心肌梗死患者左心室重构及肠道菌群的影响——一项随机对照临床研究

Effects of Tongguan Capsules(通冠胶囊)on Left Ventricular Remodeling and Gut Microbiota in Patients with Acute ST-segment Elevation Myocardial Infarction:A Randomized Controlled Clinical Study

目的观察通冠胶囊对急性心肌梗死后患者心室重构的疗效及安全性,并探讨可能的作用机制。方法收集急性ST段抬高型心肌梗死患者53例,随机分为治疗组26例和对照组27例。两组患者均行急诊经皮冠状动脉介入治疗术(PCI)后当日,对照组予以西医标准治疗方案,治疗组则在西医标准治疗方案基础上加用通冠胶囊(每次4.5 g,每日3次)口服,两组疗程均为12周。收集两组治疗前后患者超声心动图数据和粪便样本,测量计算左室射血分数(LVEF)、左室舒张末期容积指数(LVEDVi)、左室收缩末期容积指数(LVESVi)、左室质量指数(LVMi),比较两组左心室重构例数;同时对粪便样本采用16S rDNA测序,分析肠道菌群多样性、菌群组成、组间差异菌群;记录研究期间两组患者主要不良心血管事件(MACEs)发生率及不良反应;将两组患者治疗后菌群数据与LVEF、LVEDVi、LVESVi、LVM、LVMi进行Spearman相关性分析。结果本研究治疗组脱落1例,对照组脱落2例,两组最终纳入分析各25例。对照组治疗后LVEDVi、LVESVi、LVMi均高于本组治疗前(P<0.05);治疗后治疗组LVEDVi、LVESVi、LVMi均低于对照组(P<0.05)。治疗组左室重构发生5例(20.00%),对照组发生13例(52.00%),治疗组左心室重构发生率低于对照组(P=0.03)。治疗组治疗后较本组治疗前、对照组治疗后菌群丰度ACE估计量、Chao估计量均升高(P<0.05)。治疗组治疗后拟杆菌门较治疗前增多,厚壁菌门、变形菌门、髌骨菌门较治疗后减少(P<0.05)。治疗后组间比较,治疗组拟杆菌门较对照组明显增多,普雷沃菌属、琼脂杆菌属、小杆菌属、真杆菌属相对丰度上调,肠球菌属相对丰度下调(P<0.05或P<0.01)。治疗期间两组MACEs发生率及不良反应发生情况比较差异无统计学意义(P>0.05)。相关性分析结果显示,普雷沃菌属与LVEF呈正相关,与LVEDVi、LVESVi、LVM、LVMi呈负相关(P<0.01);琼脂杆菌属与LVEDVi、LVESVi呈负相关(P<0.01);肠球菌属与LVESVi呈正相关(P<0.05)。结论通冠胶囊可改善急性ST段抬高型心肌梗死患者心室重构,且安全性较好;其机制可能与调整肠道普雷沃菌属、琼脂杆菌属、小杆菌属、肠球菌属等相关菌属的富集,增加有益菌定植和菌群多样性,调整肠道菌群结构有关。

Objective To observe the efficacy and safety of Tongguan Capsule(通冠胶囊)on ventricular re⁃modeling in patients after acute myocardial infarction(AMI),and to explore the possible mechanism.Methods A total of 53 ST-segment elevation myocardial infarction(STEMI)patients were collected and randomly divided into 26 cases in the treatment group and 27 cases in the control group.The control group was given conventional therapy after percutaneous coronary intervention(PCI)for AMI,and the treatment group was given Tongguan Capsules(4.5 g each time,3 times a day)on the basis of the control group.The course of treatment was 12 weeks.Echocardiographic data and stool samples were collected from subjects before and after the intervention,and left ventricular ejection frac⁃tion(LVEF),left ventricular end-diastolic volume index(LVEDVi),left ventricular end-systolic volume index(LVESVi),left ventricular mass index(LVMi)were measured and calculated,so as to compare the number of cases of left ventricular remodeling in the two groups.At the same time,16S rDNA sequencing was performed on the stool samples to analyze the diversity of gut microbiota(GM),the composition of the GM,the GM difference between the groups;recording the incidence of major adverse cardiovascular events(MACEs)and adverse reactions of patients in the two groups during the study period;and performing Spearman´s correlation analyses of the post-treatment flora data with LVEF,LVEDVi,LVESVi,LVM,and LVMi in the two groups.Results One case fail to follow up in the treat⁃ment group and 2 cases fail to follow up in the control group,and 25 cases in each of the two groups were finally included in the analysis.LVEDVi,LVESVi,and LVMi of the control group after treatment were higher than those before treatment(P<0.05);after treatment,LVEDVi,LVESVi and LVMi in the treatment group were lower than those in the control group(P<0.05).Left ventricular remodeling occurred in 5 cases(20.00%)in the treatment group and 13 cases(52.00%)in the control group,and the incidence of left ventricular remodeling in the treatment group was lower than that in the control group(P=0.03).After treatment,the ACE estimation and Chao estimation of bacterial abundance in the treatment group were higher than that before treatment and that in the control group(P<0.05).The treatment group showed an increase in Mycobacterium anisopliae phylum and a decrease in Mycobacterium thickum,Mycobacterium anisopliae phylum,and Mycobacterium patella phylum after treatment(P<0.05).When comparing between groups after treatment,the relative abundance of Prevotella,Agathobacter,Dialister,Eubacterium coprostanoligenes group was up-reuglated and the relative abundance of Enterococcus was down-regulated in the treat⁃ment group(P<0.05 or P<0.01).There was no statistically significant difference in the incidence of MACEs and the occurrence of adverse reactions between groups during treatment(P>0.05).The results of correlation analysis showed that Prevotella were positively correlated with LVEF and negatively correlated with LVEDVi,LVESVi,LVM,and LVMi(P<0.01).Agathobacter group were negatively correlated with LVEDVi,LVESVi(P<0.01);Entero⁃coccus group were positively correlated with LVESVi(P<0.05).Conclusion Tongguan Capsules can improve ventricular remodeling in patients with acute ST-segment elevation myocardial infarction with better safety;its mecha⁃nism may be related to adjusting the enrichment of related bacteria such as Prevotella,Dialister and Enterococcus and other related bacterial genera,increasing the colonization and diversity of beneficial bacteria,and adjusting the struc⁃ture of GM.