静脉注射利多卡因后差异蛋白质的蛋白质组学分析  

Proteomic Analysis of Differentially Expressed Proteinsafter Intravenous Lidocaine

作　　者：李翔 张永海[2] 杨凡[2] 张玉[1] 杨万吉 高冉 文岳 马少玲 马汉祥[2] LI Xiang;ZHANG Yonghai;YANG Fan;ZHANG Yu;YANG Wanji;GAO Ran;WEN Yue;MA Shaoling;MA Hanxiang(The First Clinical Medical College of Ningxia Medical University,Yinchuan 750004,China;Department of Anesthesiology and Perioperative Medicine,General Hospital of Ningxia Medical University,the First Clinical Medical College of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学第一临床医学院,银川750004 [2]宁夏医科大学总医院麻醉与围术期医学科,宁夏医科大学第一临床医学院,银川750004

出　　处：《宁夏医科大学学报》2024年第6期571-576,共6页Journal of Ningxia Medical University

基　　金：宁夏自然科学基金项目(2021AAC03341)。

摘　　要：目的利用蛋白质组学技术定量分析静脉注射利多卡因(IVL)前后血清中差异蛋白质的表达。方法选取健康志愿者5例,IVL 1.5 mg·kg^(-1)后再以3 mg·(kg·h)^(-1)持续泵注30 min。IVL前和IVL后1 h各采集静脉血5 mL,通过串联质谱标记及高效液相色谱分离技术鉴定IVL后差异表达蛋白,并采用京都基因和基因组百科全书(KEGG)和基因本体论(GO)数据库分析鉴定差异蛋白的生物学信息。结果检测到IVL前后的血清中差异蛋白共15种,其中上调蛋白6种、下调蛋白9种。GO分析发现,大部分差异蛋白参与了细胞进程;亚细胞结构定位发现多数差异蛋白定位于细胞外区域及细胞质;功能富集分析发现多数蛋白参与炎性反应调节、B细胞的活化调控和蛋白质加工。上调蛋白组KEGG通路富集到p53信号通路。通过对上调组和下调组差异蛋白分析,发现差异蛋白依托泊苷诱导的2.4号蛋白(EI24)参与p53信号通路且调控钙离子浓度。结论IVL可能通过调控依托泊苷诱导的EI24和上池蛋白(SBSN)抑制肿瘤细胞的发生与发展;EI24可能通过调控细胞内钙离子浓度参与IVL产生的镇静作用。Objective To analyze the differential protein expression in serum before and after intravenous injection of lidocaine(IVL)using proteomics techniques.Methods Five healthy volunteers were enrolled in the study.5 mL of venous blood samples were taken from five volunteers before intravenous lidocaine,and then lidocaine was given intravenously at a dose of 1.5 mg·kg^(-1)for 5 minutes,followed by continuous pump infusion at 3 mg·(kg·h)^(-1)for 30 minutes.5 mL of venous blood was collected 1 h after the end of the pump.Using tandem mass tag labeling and high-performance liquid chromatography-tandem mass spectrometry,differentially expressed proteins were identified after intravenous lidocaine.The biological information of proteins was analyzed using the Kyoto encyclopedia of genes and genomes(KEGG)and gene ontology(GO)databases.Results A total of 15 differentially expressed proteins were identified before and after intravenous lidocaine.Among them,6 proteins were up-regulated and 9 proteins were down-regulated.GO analysis revealed that most differentially expressed proteins were involved in cellular processes,and subcellular localization analysis showed that most proteins were located in the extracellular region and cytoplasm.Enrichment analysis revealed that most proteins were involved in inflammation regulation,regulation of B cell activation,protein processing.KEGG pathway enrichment of the up-regulated proteins analysis revealed the p53 signaling pathway.By studying the differentially expressed proteins of the up-down-regulated group,it was found that Etoposide-induced protein 2.4(EI24)of the up-regulated group was involved in the p53 pathway and regulated the calcium ion concentration.Conclusion IVL may inhibit the development of tumor cells by regulating etoposide-induced protein 2.4(EI24)and Suprabasin.EI24 may participate in the sedative effect of IVL by regulating intracellular calcium ion concentration.

关 键 词：差异蛋白 基因本体论 富集分析 串联质谱标签 利多卡因 

分 类 号：R614[医药卫生—麻醉学]