基于代谢组学和肠道菌群研究黄芪甲苷对心肌梗死大鼠的作用

Effect of astragaloside IV on myocardial infarction in rats based on metabolomics and intestinal flora

目的研究黄芪甲苷治疗心肌梗死的量-时-效关系、药效机制通路和改善肠道菌群作用。方法采用左前降支冠状动脉结扎手术建立心肌梗死大鼠模型,给予黄芪甲苷14、28 d后,考察其量-时-效关系。利用非靶向代谢组学技术和Ingenuity Pathway Analysis数据库对效果最好的黄芪甲苷中剂量组大鼠血清进行相关代谢物分析,并采用Western blotting进行通路验证。利用肠菌多样性分析,探究黄芪甲苷对心肌梗死大鼠肠道菌群的改善作用,并对部分有益菌进行体外验证。结果黄芪甲苷可显著改善心肌梗死大鼠心功能指标(P<0.05、0.01、0.001),调控心肌梗死大鼠心肌组织白细胞介素-6(interleukin6,IL-6)/Janus激酶(Janus kinase,JAK)/信号传导和转录激活蛋白6(signal transducer and activator of transcription 6,STAT6)通路(P<0.05、0.01)。黄芪甲苷可回调心肌梗死大鼠部分菌群丰度,体外实验验证结果显示黄芪甲苷可上调有益菌Lactobacillus_johnsonii丰度。结论黄芪甲苷可改善心肌梗死大鼠心功能指标,且给药28 d、剂量为20 mg/kg时药效最为显著,其机制可能与调控IL-6/JAK/STAT6通路有关。此外,黄芪甲苷可通过改善肠道菌群辅助治疗心肌梗死。

Objective To study the dose-time-effect relationship,pharmacodynamic mechanism pathway and improvement of intestinal flora of astragaloside IV in the treatment of myocardial infarction.Methods Rat model of myocardial infarction was established using left anterior descending coronary artery ligation surgery.Astragaloside IV were administered for 14,28 d to investigate the dose-timeeffect relationship.Untargeted metabolomics techniques and Ingenuity Pathway Analysis were used to analyze relevant metabolites in serum of the most effective astragaloside IV medium-dose group,and pathway validation was performed by Western blotting.The improvement effect of astragaloside IV on the intestinal flora of rats with myocardial infarction was explored by intestinal bacterial diversity analysis,and some beneficial bacteria were verified in vitro.Results Astragaloside IV significantly improved cardiac function indexes in rats(P<0.05,0.01,0.001),regulated interleukin-6(IL-6)/Janus kinase(JAK)/signal transducer and activator of transcription 6(STAT6)pathway in myocardial tissue of rats with myocardial infarction(P<0.05,0.01).Astragaloside IV improved enterobacterial diversity,the results of in vitro experimental verification showed that astragaloside IV upregulated the abundance of beneficial bacterium Lactobacillus_johnsonii.Conclusion Astragaloside IV improves cardiac function indexes in rats with myocardial infarction,and the most significant effect was observed after 28 d of administration at a dose of 20 mg/kg,which may be related to the regulation of IL-6/JAK/STAT6 pathway.In addition,astragaloside IV can assist in the treatment of myocardial infarction by improving gut microbiota.