基于文献的四逆汤干预心肌梗死模型代谢组的生物信息学分析

Literature-based Analysis of Metabonomics Information of Sini Decoction in Intervening Myocardial Infarction Model

目的探讨四逆汤干预心肌梗死模型代谢组学产物的相互作用及生物学通路。方法从中国知网、万方数据库、维普数据库、Embase、Pubmed等数据库中检索四逆汤干预心肌梗死的代谢组学实验研究;对纳入研究的代谢产物进行汇总;信号通路分析采用KEGG,代谢产物分子注释、相关的酶或转运蛋白及其相关性质分析采用HMDB,代谢产物路径可视化采用Met PA网络软件。结果 3项研究的40种产物被纳入四逆汤干预心肌梗死模型代谢产物谱,Met PA分析显示40种代谢产物主要参与了39条代谢路径。通过通路拓扑分析选出了9条P<0.05的通路,作为四逆汤干预心肌梗死过程的代谢通路,分别是:氨酰t RNA生物合成;柠檬酸循环(TCA循环);缬氨酸、亮氨酸和异亮氨酸的生物合成;丙氨酸、天冬氨酸和谷氨酸代谢;D-谷氨酰胺和谷氨酸代谢;氮代谢;不饱和脂肪酸的生物合成;精氨酸和脯氨酸代谢;半乳糖代谢。结论四逆汤干预大鼠心肌梗死代谢组生物信息学分析显示其作用机制涉及到糖、蛋白质最终共同通路的三羧酸循环、氨基酸合成、转运等方面,体现了四逆汤作用"多因、多效、多靶点"的作用特点。

Objective To investigate the interaction of metabolic products of Sini Decoction （SD） on myocardial infarction model and their biological pathways. Methods The experimental studies of SD for the treatment of myocardial infarction were retrieved from CNKI, Wanfang Database, VIP database, EMBASE and PubMed database. The metabolic products of SD mentioned in the included studies were extracted. KEGG was used for the analysis of metabolite pathway; HMDB was applied for molecular metabolite annotation, associated enzymes or transporters and their related properties analysis, and MetPA network software was used for metabolite pathway visualization. Results A total of 3 studies were included in the analysis and 40 metabolites were involved in 39 metabolic pathways. Through tile analysis of the pathway topology, 9 pathways with P value less than 0.05 were identified as the metabolic pathways o[＇ SP in treating myocardial infarction. They were the amino acyl tRNA biosynthesis （1）, the citric, acid cycle （tricarboxylic acid cycle） （2）, valine, leucine and isoleucine biosynthesis （3）, alanine, aspartic acid and glutamic acid metabolism （4）, D-glutamine and glutamate metabolism （5）, nitrogen metabolism （6）, unsaturated fatty acid biosynthesis （7）, arginine and proline metabolism （8）, and galactose metabolism （9）. Conclusion Biological information analysis showed that the therapeutic mechanism of SP for myocardial infaction is related to the Krebs cycle （tricarboxylic acid cycle） , amino acid synthesis and transport, which are the final common pathway of sugar and protein metabolism. The results reflect the characteristics of multi-ways, multi-effects and multi-targets of Sini Decoction.