中风星蒌通腑胶囊对急性缺血性中风痰热腑实证患者肠道菌群的影响及肠道菌群与痰热腑实证的相关性探讨

Effect of Zhongfeng Xinglou Tongfu (中风星蒌通腑) Capsules on Intestinal Flora in Patients with Acute Ischemic Stroke of Tanrefushi (痰热腑实) Syndrome and Correlation Between Intestinal Flora and Tanrefushi Syndrome

目的:探讨中风星蒌通腑胶囊对急性缺血性中风痰热腑实证患者肠道菌群的影响及肠菌与痰热腑实证证候间的内在联系。方法:本研究采用随机对照的试验方法,将符合纳排标准的急性缺血性中风痰热腑实证的患者67例按随机数字表法分为对照组35例和治疗组32例,对照组给予指南规范化治疗,治疗组在对照组的基础上给予中风星蒌通腑胶囊。在入院48 h和证候转变的24 h内对两组患者进行中医证候评价和粪便采集,在入院当天和14 d进行疗效观察和生活能力评定。运用16SrDNA高通量测序对采集的样本进行肠道菌群结构和多样性分析,比较两组治疗前后肠道菌群的特征。结果:治疗组临床有效率明显高于对照组(P>0.05),与治疗前比较,两组用药后NIHSS、mRS评分、临床症状中舌质、便秘、咯痰、积分、痰热腑实证证候积分明显降低,BI总体水平明显升高(P<0.05或P<0.01)。与对照组比较,治疗组临床症状中的舌质、舌苔、脉象积分,NHISS评分和痰热腑实证证候积分明显降低(P<0.05或P<0.01)。治疗组平均(5.0±1.4)d证候转变,对照组平均(7.5±3.8)d转变(P<0.05)。在门水平上,治疗组拟杆菌门、放线菌门丰度升高,厚壁菌门、变形菌门、梭杆菌门丰度明显降低(P>0.05)。在属水平上,治疗组拟杆菌属近持平,普雷沃氏菌属、粪栖杆菌属、乳酸杆菌等益生菌丰度提高,另枝菌属、副拟杆菌属、埃希氏-志贺氏菌属等条件致病菌丰度明显降低(P>0.05)。肠菌与痰热腑实证证候的相关性分析得出粪栖杆菌属丰度与咳痰、普雷沃菌属与便干便秘呈负相关,厚壁菌门与舌质,变形菌门和咳痰,梭杆菌门与咳痰、舌质之间均成正相关(P<0.05)。结论:中风星蒌通腑胶囊治疗急性缺血性中风痰热腑实证患者临床疗效显著,该药可能通过调节肠道菌群结构,增加益生菌,减少有害菌和条件致病菌来改善中医证候,减轻神经功能缺损,从而提高卒中患者日常生活能力。

Objective:To explore the effect of Zhongfeng Xinglou Tongfu(中风星蒌通腑)Capsules on the intestinal flora of patients with acute ischemic stroke of Tanrefushi(痰热腑实)syndrome and the internal relationship between intestinal flora and Tanrefushi syndrome,so as to lay a theoretical basis for clinical practice.Methods:A randomized controlled trial(RCT)was used in this study.Sixty-seven eligible patients with acute ischemic stroke of Tanrefushi syndrome were randomly divided into a control group(n=35)and a treatment group(n=32).Patients in the control group were given standardized treatment according to the guidelines,while those in the treatment group received additional Zhongfeng Xinglou Tongfu Capsules on the basis of the therapeutic protocol of the control group.Patients in the two groups were assessed for syndrome in traditional Chinese medicine(TCM)and feces were collected within 48 hours of admission and 24 hours after the transition of syndrome.The drug efficacy was observed and the life ability was assessed on the 1st and the 14th days of admission.The structure and diversity of intestinal flora in the collected samples were analyzed by 16SrDNA high-throughput sequencing,and the characteristics of intestinal flora in the two groups before and after treatment were compared.Results:The clinical effective rate of the treatment group was higher than that of the control group(P>0.05).After treatment,the NIHSS and mRS scores,as well as the Tanrefushi syndrome score of the two groups decreased,and the overall BI level increased(P<0.05 or P<0.01).There were differences between groups in NHISS score and Tanrefushi syndrome score(P<0.01).After treatment,the scores of clinical symptoms of the two groups decreased,and the differences in tongue texture,tongue coating,and pulse manifestation of the treatment group before and after treatment were significant(P<0.05 or P<0.01).The average time for syndrome transition was(5.0±1.4)days in the treatment group and(7.5±3.8)days in the control group(P<0.05).At the phylum level,the abundance of Bacteroidetes and Actinobacteria increased in the treatment group,while the abundance of Firmicutes,Proteobacteria,and Fusobacteria decreased.The abundance of Bacteroides spp.remained unchanged.The abundance of probiotics such as Prevotella,Faecalibacterium,and Lactobacillus increased,while the abundance of opportunistic pathogens such as Alistipes,Parabacteroides,and Escherichia-Shigella decreased.The analysis of the correlation between intestinal flora and Tanrefushi syndrome revealed that the abundance of Faecalibacterium and Prevotella were negatively correlated with expectoration and constipation due to dry stool,respectively.Firmicutes was positively correlated with tongue texture,Proteobacteria with expectoration,and Fusobacteria with expectoration and tongue texture(P<0.05).Conclusion:Zhongfeng Xinglou Tongfu Capsules have significant clinical efficacy in the treatment of patients with acute ischemic stroke of Tanrefushi syndrome.This drug can improve syndrome in TCM and reduce neurological deficits by regulating the structure of intestinal flora,increasing probiotics,and reducing harmful bacteria and opportunistic pathogens,thereby improving the daily living ability of patients with stroke.