基于代谢组学及宏基因组学探讨星蒌承气汤抗脑缺血再灌注损伤的作用机制研究OA

This study uses a rat model of middle cerebral artery occlusion and reperfusion(MCAO/R)to investigate the mechanism by which Xinglou Chengqi Decoction treats cerebral ischemia-reperfusion injury,employing metabolomics and metagenomics approaches.A rat model of MCAO/R was established to evaluate the neurological function and modified neurological severity scores.Then,the brain tissue pathology,inflammatory mediators,oxidative stress,blood-brain barrier integrity,cerebral edema,and intestinal barrier function were examined to assess the pharmacological effects of Xinglou Chengqi Decoction.Metabolomics analysis of the brain tissue and metagenomics analysis of the intestinal contents were conducted to investigate the metabolism and gut microbiota regulatory mechanisms of Xinglou Chengqi Decoction.The results suggested that Xingluo Chengqi Decoction improved the neural function,reduced the severity of cerebral infarction,attenuated oxidative stress and inflammatory factor levels,boosted blood-brain barrier factor levels,minimized cerebral edema,and strengthened intestinal mucosal barrier protection,thus treating cerebral ischemia-reperfusion injury in rats.Metabolomic analysis of the brain tissue revealed that Xinglou Chengqi Decoction primarily treated ischemic stroke through 14 potential metabolic pathways,including phenylalanine,tyrosine,and tryptophan biosynthesis,valine,leucine,and isoleucine biosynthesis,and phenylalanine metabolism.Metagenomic analysis revealed that administration of Xinglou Chengqi Decoction increased the relative abundance of Firmicutes,Clostridia and Bacilli,Clostridiales and Lactobacillales,and Lachnospiraceae and Oscillospiraceae.In addition,it influenced the biosynthesis of aminoacyl-tRNA,valine,leucine,and isoleucine,along with peptidoglycan synthesis,thereby enhancing the regulatory function of the gut microbiota.Simultaneously,Xinglou Chengqi Decoction exerts therapeutic effects through the gut-brain crosstalk mediated by substances such as amino acids and fatty acids,which act within the biosynthetic and metabolic pathways.