原发性痛经气滞血瘀证患者血浆蛋白质组学研究  

Plasma proteomics study on primary dysmenorrhea patients with qi stagnation and blood stasis syndrome

作　　者：孙莹 左茜茜 刘杨杰 张拴成 杜惠兰 SUN Ying;ZUO Qian-qian;LIU Yang-jie;ZHANG Shuan-cheng;DU Hui-lan(College of Integrative Medicine,Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Institute of Integrative Medicine,Hebei University of Chinese Medicine,Shijiazhuang 050091,China;Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns,Shijiazhuang 050091,China;Beijing Emergency Medical Center,Beijing 100031,China;Collegeof Basic Medicine,Hebei University of Chinese Medicine,Shijiazhuang 050200,China)

机构地区：[1]河北中医学院中西医结合学院,石家庄050200 [2]河北中医学院中西医结合研究所,石家庄050091 [3]河北省中西医结合肝肾病证研究重点实验室,石家庄050091 [4]北京急救中心,北京100031 [5]河北中医学院基础医学院,石家庄050200

出　　处：《中华中医药杂志》2022年第11期6757-6763,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：河北中医学院研究生创新资助立项项目(No.CXZZBS2020150);河北省省级科技计划项目(No.223777158D)。

摘　　要：目的:从蛋白质表达水平探讨原发性痛经气滞血瘀证的生物学基础。方法:选择符合纳排标准的原发性痛经患者,按中医辨证分型分为气滞血瘀证组、寒凝血瘀证组,另选择健康女性作为正常组,每组8例。采用Label-free定量蛋白质组学对各组月经周期第2天的血浆样本进行分析,获取气滞血瘀证的差异表达蛋白,并进行后续生物信息学分析。结果:气滞血瘀证组与正常组筛选出67个差异表达蛋白;寒凝血瘀证组与正常组筛选出270个差异表达蛋白。经过交集映射获取气滞血瘀证差异表达蛋白47个,其中27个上调蛋白,20个下调蛋白。GO富集分析显示上调蛋白主要集中于免疫反应、代谢等过程;下调蛋白主要集中在代谢、缺氧反应等过程。蛋白结构域富集和聚类显示上调蛋白主要涉及肽聚糖结合、基质素等结构域;下调蛋白主要涉及金属肽酶家族、胰蛋白酶结构域。KEGG富集和聚类显示上调蛋白主要参与嘌呤代谢等通路。蛋白互作网络及拓扑参数分析显示中性粒细胞胶原酶(MMP8)、基质金属蛋白酶9(MMP9)、金属蛋白酶抑制剂2(TIMP2)、乳转铁蛋白(LTF)、E3泛素蛋白连接酶RBX1(RBX1)为核心差异表达蛋白。结论:气滞血瘀证的发生机制主要涉及免疫调节、炎症反应、血管内皮功能障碍、代谢紊乱、缺氧反应等生物学过程和信号通路。利用蛋白质组学寻找的5个核心差异表达蛋白可能作为气滞血瘀证的生物学标志物,对揭示气滞血瘀证的部分实质具有重要意义。Objective:To explore the biological basis of primary dysmenorrhea with qi stagnation and blood stasis syndrome from protein expression level.Methods:The patients with primary dysmenorrhea meeting the criteria of inclusion and exclusion were selected and divided into qi stagnation and blood stasis syndrome group and cold coagulation and blood stasis syndrome group according to the syndrome differentiation of TCM.In addition,healthy women were selected as the normal group,with 8 cases in each group.The plasma samples of each group on the second day of menstrual cycle were analyzed by Labelfree quantitative proteomics.The differentially expressed proteins of qi stagnation and blood stasis syndrome were obtained and analyzed by bioinformatics.Results:A total of 67 differentially expressed proteins were screened between qi stagnation and blood stasis syndrome group and normal group.A total of 270 differentially expressed proteins were screened between cold coagulation and blood stasis syndrome group and normal group.A total of 47 differentially expressed proteins of qi stagnation and blood stasis syndrome were obtained by overlapped,including 27 up-regulated proteins and 20 down-regulated proteins.GO enrichment analysis showed that up-regulated proteins were mainly concentrated in processes such as immune response,metabolism and down-regulated proteins were mainly concentrated in processes such as metabolism and hypoxia.Protein domain enrichment and clustering analyses showed that the up-regulated proteins were mainly related to peptidoglycan binding and matrixin.The downregulated proteins were mainly involved in metallopeptidase family and trypsin.KEGG enrichment and clustering analyses showed that up-regulated proteins were mainly involved in pathways such as purine metabolism.Protein-protein interaction network and topology parameters analysis showed that neutrophil collagenase(MMP8),matrix metalloproteinase 9(MMP9),metalloproteinase inhibitor 2(TIMP2),lacttransferrin(LTF),E3 ubiquitin protein ligase RBX1(RBX1)were

关 键 词：气滞血瘀证 原发性痛经 蛋白质组学 生物学基础 机制 生物学标志物 

分 类 号：R271.113[医药卫生—中医妇科学]