亚急性梭曼染毒豚鼠颈部脊髓差异表达蛋白分析  

Analysis of Differentially Expressed Proteins in the Cervical Spinal Cord of Guinea Pigs Subacutely Exposed to Soman

作　　者：靳倩 时梦 刘占彪 张毅 朱思庆 石晶晶 宗星星 陈学军 李丽琴 JIN Qian;SHI Meng;LIU Zhan-biao;ZHANG Yi;ZHU Si-qing;SHI Jing-jing;ZONG Xing-xing;CHEN Xue-jun;LI Li-qin(State Key Laboratory of NBC Protection for Civilians,Beijing 102205,China)

机构地区：[1]国民核生化灾害防护国家重点实验室,北京102205

出　　处：《中国生物工程杂志》2023年第2期64-74,共11页China Biotechnology

摘　　要：目的:利用蛋白质组学技术研究亚急性梭曼染毒豚鼠颈部脊髓中的差异表达蛋白,探讨梭曼中毒影响的主要生物学通路,为其中毒诊断、治疗及预后提供重要生物标志物。方法:以雄性成年豚鼠为研究对象,连续14天每天1次对豚鼠背部皮下注射梭曼(0.2×LD50)进行亚急性染毒;末次染毒后取颈部脊髓组织,利用蛋白质组学技术分析梭曼染毒组与对照组之间的差异表达蛋白;利用KEGG数据库对差异表达蛋白进行功能注释与通路富集分析;对重要通路中的差异蛋白进行功能分析与讨论。结果:豚鼠颈部脊髓组织中共鉴定出通过KEGG库注释的蛋白质数目为3563个;采用主成分分析和偏最小二乘法分析表明,梭曼染毒后共有407个差异表达蛋白,其中276个蛋白质表达上调,131个蛋白质表达下调,这些差异蛋白主要与代谢、遗传信息处理、环境信息处理、细胞过程、组织系统、人类疾病相关;上调蛋白质主要富集于27个通路(P<0.05),下调蛋白质主要富集于8个通路(P<0.05);上调蛋白质的主要富集通路包括吞噬体、紧密连接、细胞外基质-受体相互作用、PI3K-Akt信号通路、JAK-STAT信号通路、补体和凝血级联反应等,这些通路与24个蛋白质表达上调相关。结论:基于蛋白质组学研究,明确了亚急性梭曼染毒豚鼠颈部脊髓中出现大量差异表达蛋白,其中的6个主要通路有助于进一步阐明亚急性梭曼损伤的非胆碱能机制,其中的差异蛋白可为中毒诊断、治疗和预后提供重要的生物标志物,并为新型抗毒药物开发提供重要的理论依据。Objective:Proteomic technique was used to study the differentially expressed proteins in the cervical spinal cord of guinea pigs subacutely exposed to soman,to explore the main biological pathways affected by soman poisoning,and to provide important biomarkers for the diagnosis,treatment,and prognosis of soman poisoning.Methods:Soman(0.2×LD50)was subcutaneously injected into the back of male adult guinea pigs once a day for 14 consecutive days for subacute exposure.The cervical spinal cord tissue was collected after the final exposure,and the differentially expressed proteins between the soman and control group were analyzed by proteomics technology.Functional annotation and pathway enrichment analysis of differentially expressed proteins was performanced using KEGG database.The function of differential proteins in important pathways was analyzed and discussed.Results:A total of 3563 proteins annotated by KEGG database were identified in cervical spinal cord tissues of guinea pigs.Principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA)showed that there were 407 differentially expressed proteins after exposure to soman,of which 276 proteins were up-regulated and 131 were down-regulated.These differential proteins are mainly related to metabolism(M),genetic information processing(GIP),environmental information processing(EIP),cellular processes(CP),organismal systems(OS),and human diseases(HD).The up-regulated proteins are mainly enriched in 27 pathways(P<0.05),and the down-regulated proteins are mainly enriched in 8 pathways(P<0.05).The main enrichment pathways of up-regulated proteins include phagosome pathway,tight junction pathway,extracellular matrix(ECM)-receptor interaction pathway,PI3K-Akt signaling pathway,JAK-STAT signaling pathway,complement and coagulation cascade pathway,which are related to up regulation of 24 protein expressions.Conclusion:Based on proteomics research,it was clarified that a large number of differentially expressed proteins appeared in the cervical s

关 键 词：梭曼 蛋白质组学技术 KEGG通路分析 生物学功能 差异蛋白 

分 类 号：Q816[生物学—生物工程]