气虚血瘀证缺血中风大鼠肠道菌群对补阳还五汤有效成分的吸收影响研究

Study on Effects of Gut Microbiota of Qi Deficiency and Blood Stasis Syndrome Ischemic Stroke Rats on the Absorption of Effective Ingredients in Buyang Huanwu Decoction

目的探讨补阳还五汤在气虚血瘀证缺血中风大鼠肠道微生态环境下药物成分的吸收。方法采用力竭游泳法联合线栓法建立气虚血瘀证缺血中风大鼠模型,模型组与假手术组大鼠同时于术后1 h、24 h及48 h灌胃补阳还五汤,两组大鼠均于术后72 h取盲肠粪便行16S rRNA基因测序检测肠道菌群,采集分离血浆后运用液相色谱-质谱联用的非靶向代谢组学方法检测血浆代谢物,对肠道菌群及血浆代谢产物进行组间差异分析及关联分析。结果两组大鼠肠道菌群组成结构及血浆代谢轮廓存在明显差异,与假手术组比较,缺血中风气虚血瘀证大鼠中甜菜碱、α-紫罗兰酮、甲基没食子酸-O-硫酸盐、阿拉伯糖、棕榈酸、紫花前胡醇显著上调(P<0.05),阿糖腺苷、3-O-甲基没食子酸显著下调(P<0.05)。除3-O-甲基没食子酸外,上述其他7种药物成分的组间差异均与肠道菌群有相关性。结论气虚血瘀证缺血中风大鼠肠道菌群差异影响补阳还五汤药物成分在肠道的吸收。

Objective To explore the absorption of drug components of Buyang Huanwu Decoction under the intestinal micro-ecological environment of rats with ischemic stroke of Qi deficiency and blood stasis syndrome.Methods We established the rat models of Qi deficiency and blood stasis syndrome of ischemic stroke by exhausting swimming method combined with thread embolism.The model group and the sham operation group were gavaged with Buyang Huanwu Decoction at 1 h,24 h and 48 h after operation.After 72 hours,cecal feces samples were taken for 16S rRNA gene sequencing.After collection and separation of plasma,non-targeted metabolomics of liquid chromatography-mass spectrometry was used to detect plasma metabolites.Difference analysis and correlation analysis of intestinal flora and plasma metabolites were performed.Results There were significant differences between the 2 groups in the gut microbiota composition structure and the plasma metabolic profiles.Betaine,α-ionone,methyl gallic acid-O-sulfate,arabinose,palmitic acid,decursinol in rat models of Qi deficiency and blood stasis syndrome of ischemic stroke were significantly up-regulated(P<0.05),and vidarabine,3-O-methyl gallic acid were significantly down-regulated(P<0.05).In addition to 3-o-methyl gallic acid,the differences of other 7 drug components were correlated with gut microbiota.Conclusion The difference of gut microbiota in rats with Qi deficiency and blood stasis syndrome of ischemic stroke affected absorption of Buyang Huanwu Decoction in intestinal tract.