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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2023, Vol. 43 Issue (2/3): 64-74    DOI: 10.13523/j.cb.2209066
研究报告     
亚急性梭曼染毒豚鼠颈部脊髓差异表达蛋白分析
靳倩,时梦,刘占彪,张毅,朱思庆,石晶晶,宗星星,陈学军*(),李丽琴*()
国民核生化灾害防护国家重点实验室 北京 102205
Analysis of Differentially Expressed Proteins in the Cervical Spinal Cord of Guinea Pigs Subacutely Exposed to Soman
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
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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3 563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。
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    
Abstract:

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 3 563 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 spinal cord of guinea pigs subacutely exposed to soman, and the six main pathways were helpful to further elucidate the non-cholinergic mechanism of subacute injury. The differential expressed proteins could provide important biomarkers for the diagnosis, treatment, and prognosis of poisoning, as well as important theoretical basis for the development of new antitoxic drugs.
Key words: Soman    Proteomics    KEGG pathway analysis    Biological functions    Differential protein
收稿日期: 2022-09-26 出版日期: 2023-03-31
ZTFLH:  Q816  
通讯作者: *陈学军,李丽琴     E-mail: chenxuejun86@sina.com;llq969696@163.com
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陈学军
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引用本文:

靳倩, 时梦, 刘占彪, 张毅, 朱思庆, 石晶晶, 宗星星, 陈学军, 李丽琴. 亚急性梭曼染毒豚鼠颈部脊髓差异表达蛋白分析[J]. 中国生物工程杂志, 2023, 43(2/3): 64-74.

JIN Qian, SHI Meng, LIU Zhan-biao, ZHANG Yi, ZHU Si-qing, SHI Jing-jing, ZONG Xing-xing, CHEN Xue-jun, LI Li-qin. Analysis of Differentially Expressed Proteins in the Cervical Spinal Cord of Guinea Pigs Subacutely Exposed to Soman. China Biotechnology, 2023, 43(2/3): 64-74.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2209066    或    https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I2/3/64

图1  DIA定量蛋白质组学检测分析流程
图2  梭曼染毒组和对照组蛋白质比较Venn图
图3  梭曼染毒组和对照组的PCA分析
图4  梭曼染毒后上调(红色)蛋白和下调(蓝色)蛋白的数量
图5  梭曼染毒豚鼠颈部脊髓组织中的上调蛋白KEGG通路富集
蛋白质编号 蛋白质名称 变化幅度 基因名称 亚细胞定位 分子质量 /kDa
H0V3I8 α微管蛋白 1.429 TUBA4A 细胞质 49.9
A0A286XHV1 SEC61 1.235 SEC61A1 内质网 52.2
P01862 免疫球蛋白γ2 1.512 IGH 细胞质 36.1
H0VDM6 整合素β 1.341 ITGB1 细胞外 88.3
A0A286XZ85 β微管蛋白 1.212 TUBB2B 细胞质 49.9
A0A286XDY8 β微管蛋白 1.669 TUBB 细胞质 49.6
A0A286XLW8 Ig样结构域蛋白 3.144 MHC1 溶酶体 46.8
表1  吞噬体通路差异表达蛋白信息
蛋白质编号 蛋白质名称 变化幅度 基因名称 亚细胞定位 分子质量/kDa
H0W331 Cingulin 1.309 CGNL1 细胞质 142.9
H0V3I8 α微管蛋白 1.429 TUBA 细胞质 49.9
A0A286XCN1 Claudin 1.242 CLDN 细胞膜 22.0
A0A286XG11 神经纤维蛋白2 1.469 NF2 细胞质 69.1
H0VDM6 整合素β 1.341 ITGB1 细胞质 88.3
H0UTQ3 肌球蛋白重链9 1.562 MYH9 细胞质 226.6
表2  紧密连接通路差异表达蛋白信息
蛋白质编号 蛋白质名称 变化幅度 基因名称 亚细胞定位 分子质量 /kDa
A0A286X8W2 层粘连蛋白β1 1.260 LAMB1 细胞外 197.4
H0VFV6 层粘连蛋白β2 1.413 LAMB2 细胞外 196.9
H0VQL4 层粘连蛋白α2 1.969 LAMA2 细胞膜 341.9
A0A286XKP1 整合素α2 1.436 ITGA6 细胞质 128.4
H0VDM6 整合素β 1.341 ITGB1 细胞外 88.3
H0W6G2 硫酸乙酰肝素蛋白聚糖 2.445 HSPG2 细胞膜 456.5
A0A286XB48 重组人纤连蛋白 2.036 FN1 细胞膜 252.9
H0V077 玻连蛋白 1.553 VTN 内质网 54.9
A0A286XZP1 VI型胶原α3 10.581 COL6A3 细胞质 270
表3  细胞外基质-受体相互作用通路差异表达蛋白信息
蛋白质编号 蛋白质名称 变化幅度 基因名称 亚细胞定位 分子质量/kDa
A0A286X8W2 层粘连蛋白β1 1.260 LAMB1 细胞外 197.4
H0VFV6 层粘连蛋白β2 1.413 LAMB2 细胞外 196.9
H0VQL4 层粘连蛋白α2 1.969 LAMA2 细胞膜 341.9
A0A286XKP1 整合素α2 1.436 ITGA6 细胞质 128.4
H0VDM6 整合素β 1.341 ITGB1 细胞外 88.3
P01862 免疫球蛋白γ2 1.512 IGH 细胞质 36.1
A0A286XB48 重组人纤连蛋白 2.036 FN1 细胞膜 252.9
H0V077 玻连蛋白 1.553 VTN 内质网 54.9
A0A286XZP1 VI型胶原α3 10.581 COL6A3 细胞质 270
H0VZM6 丝氨酸/苏氨酸蛋白磷酸酶 1.245 PPP2R5 细胞质 57.3
H0UT18 受体酪氨酸激酶 1.268 EGFR 细胞膜 134.6
表4  PI3K-Akt信号通路差异表达蛋白信息
蛋白质编号 蛋白质名称 变化幅度 基因名称 亚细胞定位 分子质量/kDa
H0UT18 受体酪氨酸激酶 1.268 EGFR 细胞膜 134.6
H0W8R6 胶质纤维酸性蛋白 1.201 GFAP 线粒体 49.5
H0VXN9 信号转导和转录激活因子 1.739 Stat5b 细胞核 89.6
表5  JAK-STAT信号通路差异表达蛋白信息
蛋白质编号 蛋白质名称 变化幅度 基因名称 亚细胞定位 分子质量/kDa
Q60486 α2-巨球蛋白 1.416 A2M 细胞外 163.5
H0V077 玻连蛋白 1.553 VTN 内质网 54.9
表6  补体和凝血级联反应通路差异表达蛋白信息
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