基于粪样代谢组学研究麻黄细辛附子汤对肾阳虚外感小鼠的干预作用

Study on the Intervention Effect of Mahuang Xixin Fuzi Decoction on Kidney-Yang Deficiency Syndrome Mice Model Infected with Influenza Virus A Based on Fecal Metabolomics

目的:从粪样代谢组学角度探讨麻黄细辛附子汤对肾阳虚外感小鼠的作用机制。方法:昆明小鼠按体质量、肛温随机分为正常对照组、模型组、给药组。采用腹腔注射苯甲酸雌二醇法复制肾阳虚小鼠模型,滴鼻感染流感病毒H1N1鸡胚尿囊液建立肾阳虚小鼠外感模型,再以中药麻黄细辛附子汤干预。给药干预6 d,末次给药12h后取小鼠粪便,对小鼠粪样进行HPLC-MS分析,然后使用R语言、MPP、SIMCA-P等软件对数据进行处理。结果:模型组、正常对照组和给药组小鼠代谢物有明显的差异,利用Metpa数据平台分析发现并鉴定了5个潜在的生物标志物,分别为犬尿氨酸、酮戊二酸等,这些生物标志物主要涉及色氨酸代谢、柠檬酸代谢等5条代谢通路。结论:与正常对照组相比,模型组小鼠内源性物质犬尿氨酸和酮戊二酸等含量发生明显变化。麻黄细辛附子汤给药作用后,代谢通路发生逆转并趋于正常状态,说明麻黄细辛附子汤可能从改善氨基酸代谢和能量代谢等方面发挥作用。

Objective： To explore the mechanism of Mahuang Xixin Fuzi decoction on kidney-yang deficiency syndrome mice model from the perspective of fecal metabolomics. Methods： According to the body weight and rectal temperature of the KM mice were randomly divided into normal group,model group,Mahuang Xixin Fuzi decoction groups. By intraperitoneal injection of estradiol benzoate copy model of kidney yang deficiency syndrome,and used the establishment of exogenous mouse model infected with influenza virus H1 N1,and then gave Mahuang Xixin Fuzi decoction of traditional Chinese medicine intervention. Mahuang Xixin Fuzi decoction group was intervened by drug once a day for 6 d,the faeces samples were collected from each mice 12 h after the last administration in the three groups. HPLC-MS analysis was carried out on mice feces,and then processing the data using the R language,MPP,SIMCA-P software. Results： There were significant differences in three group. The five potential biomarkers were found and identified,these are trespectively kynurenic acid,ketone glutaric acid,which mainly involved lubricious ammonia acid metabolism,lemon acid metabolism etc five metabolic pathways. Conclusion： Compared with the normal group,the mice of model group have significant differences in canine urine acid and ketoglutaric acid metabolites. After the group intervened by Mahuang Xixin Fuzi decoction,the pathways are changed and then to the normal condition,which can explain that Mahuang Xixin Fuzi decoction probably play a role to change the aspect of amino acid metabolism and energy metabolism.