成都中医药大学学报2025，Vol.48Issue(5)：21-28,8.DOI:10.13593/j.cnki.51-1501/r.2025.05.005
肠道代谢物介导时间限制性进食改善高盐性血瘀证的机制研究
Mechanism by Which Gut Metabolites Mediate the Ameliorative Effect of Time-Restricted Eating on Salt-Induced Blood Sta-sis Syndrome
摘要
Abstract
Objective:To investigate the efficacy of time-restricted feeding(TRF)in ameliorating high-salt-induced blood stasis syn-drome in rats,analyze its effects on intestinal metabolites,and explore the underlying mechanisms of TRF intervention.Methods:Thirty Wistar rats(15 males and 15 females)were randomly divided into three groups(n=10 per group):normal control group,model group,and TRF group.The normal control group received a standard diet and water ad libitum.The model and TRF groups were fed a high-salt diet(containing 8％sodium chloride)with free access to water.The TRF group was allowed free access to food only be-tween 8:00 AM and 4:00 PM for 8 weeks.After sacrifice,blood rheology,coagulation parameters(APTT,PT,TT,FIB),and patho-logical changes in the thoracic aorta and colon were evaluated using hematoxylin-eosin(H&E)staining.Gut microbiota composition was assessed via 16S rDNA high-throughput sequencing,and fecal metabolites were profiled using UHPLC-QE-MS-based untargeted metabolomics to determine the effects of TRF on gut microbiota metabolism.Results:Compared with the control group,the model group exhibited significantly increased whole blood viscosity(P＜0.001)and plasma viscosity(P＜0.05);significantly shortened APTT and PT(P＜0.05);and significantly prolonged TT and increased FIB(P＜0.05).H&E staining of the thoracic aorta re-vealed vascular structural damage,endothelial necrosis,and mild inflammatory cell infiltration in the model group.Compared to the model group,the TRF group showed significantly decreased whole blood viscosity(P＜0.005)and plasma viscosity(P＜0.01);significantly prolonged APTT and PT(P＜0.05);and significantly shortened TT and decreased FIB(P＜0.05).Microbiota analysis revealed a significant decrease in the relative abundance of Firmicutes(P＜0.001)and a significant increase in Bacteroidetes(P＜0.001)in the model groupversus controls.TRF significantly increased the relative abundance of Firmicutes(P＜0.05)and decreased Bacteroidetes(P＜0.05)compared to the model group.Compared with the control group,the model groupshowed significantly in-creased relative abundances of"uncultured_Bacteroidales_bacterium",prevotellaceae_UCG_001,unclassified_Erysipelotrichaceae,Muribaculum,and Turicibacter(P＜0.01),while the relative abundance of"uncultured_Bacteroidales_bacterium"was significantly decreased(P＜0.01).TRF intervention significantly upregulated fecal metabolites in high-salt blood stasis model rats,including Gla-brin A,1-hydroxy-5,5-dimethylpyrrolidin-2-ol,4-vinylphenol sulfate,Basellasaponin A,deoxythymidylic acid,betaine,5-hydroxyin-doleacetic acid,and arachidonic acid(P＜0.01),and significantly downregulated PA(8:0/18:1(12Z)-2OH9,10)(P＜0.01).Conclusion:Time-restricted feeding ameliorates high-salt-induced blood stasis by remodeling gut microbiota structure(increasing the Firmicutes/Bacteroidetes ratio)and promoting the generation of protective metabolites(e.g.arachidonic acid for anti-inflammation,betaine for osmoregulation).This provides evidence for a gut microbiota-metabolite axis mechanism underlying TRF intervention in salt-sensitive cardiovascular diseases.关键词
限时进食法/高盐/血瘀证/肠道菌群代谢物Key words
Time-restricted feeding/High-salt/Blood stasis syndrome/Gut microbiota metabolites分类
医药卫生引用本文复制引用
聂开迪,汪杰,刘佼,夏丽娜..肠道代谢物介导时间限制性进食改善高盐性血瘀证的机制研究[J].成都中医药大学学报,2025,48(5):21-28,8.基金项目
国家自然科学基金面上项目(82274384) （82274384）
四川省自然科学基金面上项目(2024NSFSC0717) （2024NSFSC0717）
