基于血清代谢组学技术考察通阳化浊方与四妙勇安汤治疗冠心病模型家兔的作用机制＊

目的 通过血清代谢组学技术,考察通阳化浊方与四妙勇安汤在治疗冠心病家兔中的作用机制。方法 40只雄性白兔,随机分为空白组、模型组、通阳化浊方组与四妙勇安汤组4组,每组10只。空白组正常饮食,模型组给予高脂饲料喂养至第8周,于第4周结束后,用球囊法手术损伤实验兔的右侧颈总动脉;在模型组基础上,两个实验组分别在术后,灌胃给予通阳化浊方和四妙勇安汤,连续4周,每日1次。给药结束后,模型组与实验组每组抽取3只家兔,采集全血后,用LC-MS技术进行血清代谢组学检测,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45和27个差异化合物,通阳化浊方组涉及18条代谢通路,根据Impact值 > 0.05筛选出5条主要代谢通路,包括精氨酸和脯氨酸代谢、组氨酸代谢、牛磺酸和牛磺酸代谢、精氨酸生物合成和α-亚麻酸代谢;四妙勇安汤组涉及11条代谢通路,筛选出2条主要代谢通路分别为牛磺酸和牛磺酸代谢、组氨酸代谢。结论 通阳化浊方与四妙勇安汤在治疗冠心病模型家兔的过程中存在差异性代谢产物,干预相应的代谢通路可能会对药物在模型中的作用产生影响。

Mechanism of the Effect of Tongyang Huazhuo Decoction and Simiao Yongan Decoction in the Treatment of Rabbits with Coronary Heart Disease Model Based on Serum Metabolomics Technology

Objective To explore the mechanism of Tongyang Huazhuo Decoction and Simiao Yongan Decoction in the treatment of rabbits with coronary heart disease by serum metabolomics techniques.Methods 40 male white rabbits were randomly divided into 4 groups, namely the blank group, control group, Tongyang Huazhuo Decoction group and Simiao Yongan Decoction group, with 10 in each group. The blank group had a normal diet; The control group was given a high-fat diet until the 8^th week. At the end of the 4^th week, we surgically injure the rabbits?? right common carotid artery using the balloon method. On the basis of the control group, the 2 experimental groups were given Tongyang Huazhuo Decoction and Simiao Yongan Decoction by gavage once a day for 4 weeks, respectively. After the drug administration, 3 rabbits were drawn from each group of the model and experimental groups, and whole blood was collected. Through LC-MS technology, PCA and OPLS-DA analysis,we used serum metabolites to find metabolites and metabolic pathways with different expressions.Results Compared with control group, we identified 45 and 27 characteristic metabolites in Simiao Yongan Decoction and Tongyang Huazhuo Decoction groups respectively. Tongyang Huazhuo Decoction group involved 18 metabolic pathways, according to the Impact value > 0.05, we find out 5 major metabolic pathways, including Arginine and Proline metabolism, Histidine metabolism, Arginine biosynthesis, Taurine and Hypotaurine metabolism, alpha-linolenic acid metabolism; Simiao Yongan Decoction group involved 11 metabolic pathways, and 2 major metabolic pathways were selected as Taurine and Hypotaurine metabolism, Histidine metabolism respectively.Conclusion Differential metabolites exist between Simiao Yongan Decoction and Simiao Yongan Decoction in the treatment of rabbits with a model of coronary heart disease, and intervention in the corresponding metabolic pathways may have an effect on the action of the drugs in the model.