基于肠道菌群探讨四逆汤治疗慢性心力衰竭心阳虚证的作用机制  

Mechanism of Sini Decoction(四逆汤)in Treating Chronic Heart Failure with Xinyangxuzheng(心阳虚证)Based on Intestinal Flora

作　　者：张曦宁 董振华 赵震宇 杜刘思 胡志希[1,2] 李琳[1,2] ZHANG Xining;DONG Zhenhua;ZHAO Zhenyu;DU Liusi;HU Zhixi;LI Lin(Hunan University of Chinese Medicine,Changsha 410208;Institute of Traditional Chinese Medicine Diagnostics,Hunan University of Chinese Medicine,Changsha 410208)

机构地区：[1]湖南中医药大学,长沙410208 [2]湖南中医药大学中医诊断研究所,长沙410208

出　　处：《中药药理与临床》2024年第1期8-16,共9页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:82274412);湖南省自然科学基金项目(编号:2023JJ30453);中医学一流学科开放基金(编号:2021ZYX03);长沙市自然科学基金(编号:kq2208185);湖南省中医药科研项目(编号:B2023045)。

摘　　要：目的:检测慢性心力衰竭大鼠以四逆汤治疗前后肠道菌群的变化,探讨四逆汤治疗慢性心衰心阳虚证作用机制。方法:24只大鼠分为正常对照组、模型对照组、四逆汤2.8 g/kg组、美托洛尔0.01 g/kg组。造模大鼠腹腔注射阿霉素1.5 mL/kg,1次/w,连续7 w,制备慢性心衰心阳虚证模型。造模成功后,各组灌胃相应药物或者蒸馏水,1次/d,连续21 d。干预结束后取出新鲜粪便,进行高通量测序分析。结果:与正常对照组比较,模型对照组大鼠左心室射血分数(LVEF)和左心室缩短分数(LVFS)均显著下降(P<0.01),血清中NT-proBNP含量显著升高(P<0.01),肠道菌群中Patescibacteria与放线菌门比率显著降低(P<0.01),罗姆布茨菌比例下降(P<0.05),梭状芽胞杆菌、苏黎世杆菌属、Adlercreutzia属、Bacteroides、Bacteroides_Pectinophilus等有害菌或条件致病菌成为优势菌,肠道菌群结构、优势菌及各菌群丰度产生变化;与模型对照组比较,四逆汤2.8 g/kg组大鼠LVEF、LVFS显著升高(P<0.01),血清中NT-proBNP含量显著降低(P<0.01),肠道菌群中Patescibacteria与放线菌门比率明显升高(P<0.05),罗姆布茨菌、NK4A214_group、克里斯滕森菌属、候选单胞生糖菌属、norank_f_UCG-010比例明显升高(P<0.05),双歧杆菌属、苏黎世杆菌属、未分类的厚壁菌比例显著降低(P<0.05),粪杆菌真核菌属、罗姆布茨菌、Candidatus_Saccharimonas、Peptococcaceae、NK4A214、UCG-010、克里斯滕森菌、Faecalibaculum等有益菌成为优势菌,肠道菌群结构、优势菌及各菌群丰度产生正向调整,促进有益菌生长,抑制有害菌生长,这可能与四逆汤治疗心衰心阳虚证的作用机制有潜在关联。结论:四逆汤可能通过有效调整慢性心衰心阳虚证大鼠肠道菌群的结构、优势菌群及各菌群丰度从而改善心衰。Objective:To investigate the changes in intestinal flora before and after the treatment with Sini Decoction(四逆汤)in rats with chronic heart failure(CHF)and explore the mechanism of Sini Decoction in treating CHF with Xinyangxuzheng(心阳虚证).Methods:Twenty-four rats were divided into a normal control group,a model control group,a Sini Decoction(2.8 g/kg)group,and a metoprolol(0.01 g/kg)group.The rats for modeling underwent intraperitoneal injection of doxorubicin at 1.5 mL/kg once a week for 7 consecutive weeks to induce a CHF model with Xinyangxuzheng.After successful modeling,each group was orally administered the corresponding drugs or distilled water once a day for 21 days.Fresh fecal samples were collected after intervention for high-throughput sequencing analysis.Results:Compared with the normal control group,the model control group showed significant decreases in left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P<0.01),and a significant increase in serum NT-proBNP content(P<0.01).Furthermore,the ratio of Patescibacteria to Actinobacteria in the intestinal flora was significantly reduced(P<0.01),the proportion of Romboutsia decreased(P<0.05),and harmful or conditionally pathogenic bacteria such as Clostridium,Turicibacter,Adlercreutzia,Bacteroides,Bacteroides_Pectinophilus and so on became dominant.leading to changes in the structure,dominant bacteria,and abundance of various bacterial groups in the gut.Compared with the model control group,the Sini Decoction(2.8 g/kg)group exhibited significant increases in LVEF and LVFS(P<0.01),a significant decrease in serum NT-proBNP content(P<0.01),a significant increase in the ratio of Patescibacteria to Actinobacteria in the intestinal flora(P<0.05),and positive adjustments in the structure,dominant bacteria,and abundance of various bacterial groups in the gut.the proportions of Romboutsia,NK4A214_group,Christensenellaceae_R7_group,Candidatus_Saccharimonas,norank_f_UCG-010 were significantly higher(P<0.05),the proporti

关 键 词：四逆汤 慢性心力衰竭 肠道菌群 

分 类 号：R285.5[医药卫生—中药学]