通阳化浊方与四妙勇安汤干预动脉粥样硬化模型家兔的粪便代谢组学比较研究＊

目的 通过粪便代谢组学技术,考察通阳化浊方与四妙勇安汤在治疗动脉粥样硬化家兔中的作用机制。方法 40只白兔,雄性,每组10只,随机分为4组,包括空白组、模型组、通阳化浊方组与四妙勇安汤组。空白组给予8周正常饮食;模型组和两个给药组以高脂饲料喂养,4周后,用球囊法手术损伤实验兔的右侧颈总动脉;两个给药组在术后,分别每日1次灌胃给予通阳化浊方和四妙勇安汤至第8周。模型组与实验组每组抽取3只家兔,采集粪便后,用LC-MS技术进行粪便代谢组学检测,运用PCA与OPLS-DA分析法来寻找差异性表达的代谢物和代谢途径。结果 相较于模型组,通阳化浊方与四妙勇安汤组分别存在59和48个差异化合物,通阳化浊方组涉及20条代谢通路,5条主要代谢通路分别为苯丙氨酸、酪氨酸和色氨酸的生物合成、花生四烯酸代谢、视黄醇代谢、苯丙氨酸代谢以及淀粉和蔗糖代谢;四妙勇安汤组涉及15条代谢通路,4条主要代谢通路包括酪氨酸和色氨酸的生物合成、苯丙氨酸代谢、苯丙氨酸、亚油酸代谢和花生四烯酸代谢。结论 在治疗动脉粥样硬化模型家兔的过程中,通阳化浊方与四妙勇安汤在粪便代谢组学方面存在差异性代谢产物,干预相应的代谢通路,可能会对药物的作用产生影响。

A Comparative Study of Fecal Metabolomics between Tongyang Huazhuo Formula and Simiao Yong'an Decoction Intervention in the Rabbit Model with Atherosclerosis

Objective To investigate the mechanism of action of Tongyang Huazhuo Formula and Simiao Yong''an Decoction in the treatment of atherosclerotic rabbits by fecal metabolomics techniques.Methods 40 male white rabbits were randomly divided into 4 groups with 10 rabbits in each group, including blank group, model group, Tongyang Huazhuo Formula ecoction group and Simiao Yong''an Decoction group. The blank group was given normal diet for 8 weeks. Model group and two administration groups were fed with high fat diet. After 4 weeks, the right common carotid artery of experimental rabbits was damaged by balloon operation. The two groups were given Tongyang Huazhuo Formula and Simiao Yong''an Decoction once a day after operation until the 8^th week. Three rabbits were selected from each group of the model group and the experimental groups. Feces were collected, and fecal metabolomics was detected by LC-MS technology. PCA and OPLS-DA analysis were used to find metabolites and metabolic pathways of different expression.Results Compared with model group, there are 59 and 48 differential compounds respectively in Tongyang Huazhuo Formula group and Simiao Yong''an Decoction group. Tongyang Huazhuo Formula group involves 20 metabolic pathways, and the five main metabolic pathways are the biosynthesis of phenylalanine, tyrosine and tryptophan, arachidonic acid metabolism, retinol metabolism, phenylalanine metabolism, and starch and sucrose metabolism; Simiao Yong''an Decoction group involved 15 metabolic pathways, and the four main metabolic pathways included phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism linoleic acid metabolism and aracidonic acid metabolism.Conclusion In the process of treating atherosclerosis model rabbits, Tongyang Huazhuo Decoction and Simiao Yong''an Decoction have different metabolites in fecal metabolomics, and intervention in the corresponding metabolic pathway may affect the effect of the drug.