中国现代中药2025，Vol.27Issue(5)：878-889,中插8,13.DOI:10.13313/j.issn.1673-4890.20250113007
基于代谢组学及肠道菌群的水蛭治疗气滞血瘀证大鼠作用机制探究
Mechanism of Hirudo in Treating Qi Stagnation and Blood Stasis Syndrome in Rats Based on Metabolomics and Intestinal Flora
摘要
Abstract
Objective:To explore the potential mechanism of Hirudo in treating qi stagnation and blood stasis syndrome(QSBSS)in rats by combining metabolomics and intestinal flora.Methods:The rat model of QSBSS was prepared by multi-factor composite modeling method of restraints combined with tail clamping,ice water bathing,and water deprivation,and the modeling lasted for 24 consecutive days.Rats were randomized into the blank,model,Hirudo(3.0 g·kg-1),and positive drug(Xuefu Zhuyu Oral Liquid,10 mL·kg-1)groups and administerted with corresponding agents 30 min before modeling once daily.During the modeling process,the general state of rats was observed daily,and the blood and intestinal contents of the rats were collected the next day after the last modeling.The four coagulation indexes were determined by an automatic coagulation analyzer.Blood rheology was determined by an automatic blood rheology detector.The plasma metabolites were detected by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS),and intestinal flora of rats was analyzed by 16S rRNA sequencing.The correlation analysis was carried out between differential metabolites and differential microbial groups.Results:The rats in the model group showed QSBSS-related manifestations such as irritability,purple and dark tongue,thickening and extension of sublingual veins,decreased activity,and reduced food intake,and the above symptoms were alleviated after drug interventions.The modeling led to increases in the viscosity and fibrinogen(FIB)of whole blood(P<0.01)and decreases in activated partial thromboplastin time(APTT),prothrombin time(PT),and thrombin time(TT)(P<0.01),and the changes were significantly diminished after drug interventions.A total of 20 differential metabolites were screened by metabolomics,among which eicosapentaenoic acid,vitamin A,tretinoin,alpha-ketoglutaric acid,and guanidineacetic acid were the key biomarkers.The abundance and diversity of intestinal flora in the model group decreased.Specifically,the relative abundance of Lactobacillus decreased(P<0.01)and that of Bacteroides increased(P<0.01),which were significantly reversed after drug interventions.The results of Spearman analysis showed that vitamin A and eicosapentaenoic acid had strongly positive correlations with Lactobacillus,and guanidinoacetic acid had a strongly negative correlation with Bacteroides.The differential metabolites and differential microbial groups were mainly enriched in the energy metabolism,nucleotide metabolism,amino acid metabolism,and lipid metabolism pathways.Conclusion:Hirudo may treat QSBSS by regulating the intestinal flora structure and plasma metabolites,and there are significant correlations between intestinal flora and plasma metabolites.关键词
水蛭/气滞血瘀证模型/代谢组学/肠道菌群Key words
Hirudo/model of qi stagnation and blood stasis syndrome/metabolomics/intestinal flora分类
医药卫生引用本文复制引用
梅姗姗,黄苗苗,黄楚莹,方可欣,何光宗,高梦菲,杨瑶珺..基于代谢组学及肠道菌群的水蛭治疗气滞血瘀证大鼠作用机制探究[J].中国现代中药,2025,27(5):878-889,中插8,13.基金项目
北京市自然科学基金面上基金项目(7222275) （7222275）
