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