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7w,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.
Abstract
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 Pa-tescibacteria 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 sig-nificantly higher(P＜0.05),the proportions of Bifidobacterium,Turicibacter,and unclassified_p_Firmicutes were significantly lower(P＜0.05),and the beneficial bacteria of the norank_f__Eubacterium_coprostanoligenes,Romboutsia,Candidatus_Saccharimonas,Peptococcace-ae,NK4A214,UCG-010,Christensenellaceae_R7_group,Faecalibaculum and so on became dominant.Moreover,the growth of beneficial bacteria was promoted and the growth of harmful bacteria was inhibited,suggesting a potential association with the mechanism of Sini Decoc-tion in treating CHF with Xinyangxuzheng.Conclusion:Sini Decoction may improve CHF by effectively adjusting the structure of intestinal flora,dominant bacterial groups,and the abundance of various bacterial groups in CHF rats with Xinyangxuzheng.
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