消肿止痛合剂抗皮瓣缺血再灌注损伤的代谢组学作用机制  

Mechanism of Xiaozhong Zhitong Mixture against ischemia-reperfusion injury of skin flaps based on metabolomics

作　　者：何波 何志军[2] 刘涛 马岁录 He Bo;He Zhijun;Liu Tao;Ma Suilu(College of Traditional Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730030,Gansu Province,China;Department of Foot and Ankle Orthopedics,Gansu Hospital of Traditional Chinese Medicine,Lanzhou 730050,Gansu Province,China)

机构地区：[1]甘肃中医药大学中医临床学院,甘肃省兰州市730030 [2]甘肃省中医院足踝骨科,甘肃省兰州市730050

出　　处：《中国组织工程研究》2023年第23期3653-3659,共7页Chinese Journal of Tissue Engineering Research

基　　金：甘肃省中医药项目(GZKZ-2020-2),项目负责人:何志军;兰州市人才创新创业专项(2019-RC-63),项目负责人:何志军;国家自然科学基金(81660802),项目负责人:何志军。

摘　　要：背景:课题组前期研究证实消肿止痛合剂能够缓解皮瓣缺血再灌注损伤,但关于其代谢组学方面的作用机制研究尚未报道。目的:探究消肿止痛合剂抗大鼠皮瓣缺血再灌注损伤的作用机制。方法:建立大鼠皮瓣缺血再灌注损伤模型,利用代谢组学相关技术分析正常大鼠、模型大鼠以及给予消肿止痛合剂干预后大鼠血清样本中内源性代谢物的差异,检索及鉴定生物标志物并构建代谢通路。结果与结论:消肿止痛合剂能够显著减轻皮瓣缺血再灌注损伤模型大鼠皮瓣组织的病理变化。筛选出显著性差异代谢物丙二酸和3-(3羟基苯基)丙酸,将差异代谢物导入在线数据库MetaboAnalyst 4.0及KEGG数据库进行代谢通路分析,得出消肿止痛合剂干预大鼠皮瓣缺血再灌注损伤后代谢的途径涉及嘧啶代谢、苯基丙氨酸代谢等代谢通路。结果表明,消肿止痛合剂通过对嘧啶代谢、苯基丙氨酸等代谢通路对大鼠皮瓣缺血再灌注损伤进行调节,为阐明消肿止痛合剂治疗大鼠皮瓣缺血再灌注损伤的作用机制提供了理论依据。BACKGROUND:Previous studies have confirmed that Xiaozhong Zhitong Mixture can alleviate ischemia-reperfusion injury of skin flaps,but its metabolomic mechanism has not been reported.OBJECTIVE:To explo re the mechanism of Xiaozhong Zhitong Mixture against ischemia-reperfusion injury of rat skin flaps.METHODS:A rat skin flap ischemia-reperfusion injury model was established.Related metabolomics techniques were used to analyze the endogenous levels of metabolite samples from normal rats,model rats and rats after intervention with Xiaozhong Zhitong Mixture.Relevant biomarkers were retrieved and identified and metabolic pathways were then constructed.RESULTS AND CONCLUSION:Xiaozhong Zhitong Mixture could significantly reduce the pathological changes of skin flap tissue in rats with skin flap ischemiareperfusion injury.Significantly differential metabolites,including malonic acid and 3-(3-hydroxyphenyl)propionic acid,were identified and imported into MetaboAnalyst 4.0 and KEGG databases for metabolic pathway analysis.After intervention,the metabolic pathways of Xiaozhong Zhitong Mixture included pyrimidine metabolism and phenylalanine metabolism.To conclude,Xiaozhong Zhitong Mixture improves ischemia-reperfusion injury of rat skin flap by regulating the metabolic pathways such as pyrimidine and phenylalanine metabolic pathways,which thereby provides a theoretical basis for clarifying the mechanism of Xiaozhong Zhitong Mixture in the treatment of ischemia-reperfusion injury of rat skin flap.

关 键 词：消肿止痛合剂 代谢组学 皮瓣缺血再灌注 丙二酸 3-(3羟基苯基)丙酸 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R285.5