| 石楚雅,师金花,薄艳萍,等.基于 Astral-DIA蛋白质组学技术探讨慢性大量饮酒无酒精性肝病者血清蛋白变化及意义[J].安徽医药,2026,30(10):2079-2084. |
| 基于 Astral-DIA蛋白质组学技术探讨慢性大量饮酒无酒精性肝病者血清蛋白变化及意义 |
| Explore the changes and significance of serum proteins in chronic heavy drinkers without alcoholic liver disease based on the Astral-DIA proteomics technology. |
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| DOI：10.3969/j.issn.1009-6469.2026.10.033 |
| 中文关键词: 酒精性肝病 饮酒 Astral-DIA蛋白质组学 补体激活途径 补体凝血级联信号通路 烟酰胺 |
| 英文关键词: Alcoholic liver disease Alcohol drinking Astral-DIA proteomics Complement activationpathway Complement and coagulation cascade signaling pathway Nicotinamide |
| 基金项目:山西省教育厅高校科技创新计划项目( 2023L093) |
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| 中文摘要: |
| 目的基于 Astral数据非依赖性采集( Astral-DIA)蛋白质组学技术挖掘慢性大量饮酒有无酒精性肝病者体内差异蛋白和意义。方法前瞻性研究。纳入山西医科大学附属汾阳医院 2023年 3月至 2024年 5月慢性大量饮酒无酒精性肝病者 13例(研究组)和慢性大量饮酒有酒精性肝病者 13例(疾病组)收集所有参与者血液离心后分离血清，分别在两组中挑选 3例血清样品进行 Astral-DIA蛋白质组学检测筛选出差异表达蛋白，结，合多个数据库对差异表达蛋白进行基因本体论(GO)功能富集分析，依托 GO和京都基因与基因组百科全书( KEGG)并使用 STRING数据库进行蛋白 -蛋白互作( PPI)网络分析，筛选出关键差异蛋白，最后将关键差异蛋白在另外 10例研究组和10，例疾病组中进行酶联免疫吸附分析( ELISA)验证。结果研究组和疾病组有 122个差异蛋白，根据 GO功能和 KEGG通路富集分析显示，差异蛋白主要与经典途径补体激活、调节免疫反应等生物学过程等相关，涉及的信号通路包括补体与凝血级联信号通路和烟酸和烟酰胺代谢通路。 PPI网络显示，血浆蛋白酶 C1抑制剂(C1-INH)、补体 C1s亚单位重链、凝血因子 V及纤维蛋白原 γ链蛋白为关键蛋白。 ELISA结果显示，与疾病组比较，研究组中 C1-INH、烟酰胺磷酸核糖转移酶( NAMPT)表达水平显著增高［( 218.27±14.51)mg/L比( 97.96±5.87)mg/L；(205.31±16.25)mg/L比( 121.13±14.15)mg/L，P<0.001］。结论 C1-INH和 NAMPT是长期饮酒而无酒精性肝病者体内的保护性蛋白，分别通过调节补体与凝血级联信号通路和烟酸与烟酰胺代谢通路使肝细胞免受酒精损害。 |
| 英文摘要: |
| Objective To identify differentially expressed proteins and explore their significance in individuals with chronic heavyalcohol consumption, with or without alcoholic liver disease (ALD), using Astral Data-Independent Acquisition (Astral-DIA) proteomics. Methods Prospective study. A total of 13 patients with chronic heavy alcohol consumption without ALD (study group) and 13 patientswith chronic heavy alcohol consumption with ALD (disease group) at Fenyang Hospital Affiliated to Shanxi Medical University fromMarch 2023 to May 2024 were enrolled. Blood samples were collected from all participants, and serum was isolated after centrifuga-tion. Three serum samples were randomly selected from each group for Astral-DIA proteomic analysis to screen for differentially expressed proteins (DEPs). Functional enrichment analyses of DEPs were performed using gene ontology (GO) and the Kyotoencyclopedia of genes and genomes (KEGG) pathway databases. Protein-protein interaction (PPI) networks were constructed using theSTRING database to identify key differential proteins. Subsequently, the key differential proteins were validated by enzyme-linked immunosorbent assay (ELISA) in the remaining 10 cases from each group. Results A total of 122 differentially expressed proteinswere identified between the study group and the disease group. GO functional annotation and KEGG pathway enrichment analysesrevealed that these differentially expressed proteins were primarily involved in biological processes such as classical pathway complementactivation and regulation of immune response. The significantly enriched signaling pathways included the complement and coagulationcascades, as well as the nicotinate and nicotinamide metabolism pathway. PPI network analysis identified plasma protease C1 inhibitor(C1-INH), complement C1s subcomponent heavy chain, coagulation factor V, and fibrinogen gamma chain as hub proteins. Furthermore,ELISA results demonstrated that the expression levels of C1-INH and nicotinamide phosphoribosyltransferase (NAMPT) in the studygroup were significantly elevated compared with the disease group [(218.27 ± 14.51) mg/L vs. (97.96 ± 5.87) mg/L ; (205.31 ± 16.25) mg/L vs. (121.13 ± 14.15) mg/L, P<0.001].Conclusion C1-INH and NAMPT are protective proteins in patients with chronic heavyalcohol consumption but without ALD, which protect hepatocytes from alcohol-induced damage through regulation of the complementand coagulation cascades signaling pathway and the nicotinate and nicotinamide metabolism pathway, respectively. |
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