酒精性肝病患者脂代谢相关差异蛋白的定量分析  

Quantitative analysis of lipid metabolism-related differential proteins in patients with alcoholic liver disease

作　　者：张莹[1] 刘芳[1] 时红林[1] 陈德喜[1] 时红波[1] Zhang Ying;Liu Fang;Shi Honglin;Chen Dexi;Shi Hongbo(Beijing You An Hospital Afiliated to Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京佑安医院、北京市肝病研究所,北京100069

出　　处：《中华肝脏病杂志》2023年第3期293-299,共7页Chinese Journal of Hepatology

基　　金：北京市自然科学基金(M22030)。

摘　　要：目的应用串联质谱标记(TMT)技术筛选和鉴定酒精性肝病(ALD)患者肝脏组织中的差异蛋白,对脂代谢相关蛋白和通路进行分析,探索其功能及生物学过程。方法收集符合纳入标准的肝脏组织,筛选出酒精性肝硬化患者样本8例,正常对照组样本3例。采用TMT技术筛选差异蛋白并进行富集信号通路分析和蛋白质网络互作分析,探索其参与的生物学过程。结果蛋白质组学分析鉴定出2组资料中有2741种差异蛋白具有统计学意义(P<0.05),以P<0.05且|log2(foldchange)|>1的标准筛选出差异表达蛋白106种,与对照组相比,ALD组上调蛋白12种,下调蛋白94种。其中,与脂代谢相关的上调差异蛋白有2种,下调差异蛋白有14种。生物信息学分析结果显示这些蛋白在脂代谢中主要参与了脂质转运,脂肪酶活性的调节,脂肪酸结合以及胆固醇代谢等生物学过程,并与过氧化物酶体增殖物激活受体信号通路、胆固醇代谢、甘油三酯代谢及脂肪细胞内脂解的调节等脂代谢相关信号通路密切相关。结论16种脂代谢相关差异蛋白可能是ALD发病机制中的关键蛋白。Objective To screen and identify differential proteins,analyze lipid metabolism-related proteins and pathways,and explore their functions and biological processes in liver tissue of patients with alcoholic liver disease using tandem mass tag(TMT)labeling technology.Methods Liver tissues that met the inclusion criteria were collected.Eight samples from patients with alcoholic cirrhosis and three samples from the normal control group were screened out.The TMT technique was used to screen differential proteins,perform signaling pathway enrichment analysis,and analyze protein interaction networks to explore the biological processes involved in them.Results Proteomic analysis identified 2741 kinds of differentially expressed proteins in the two groups of data with statistical significance(P<0.05).The standard criteria of P<0.05 and|log2(foldchange)|>1 had screened out 106 kinds of differentially expressed proteins.Compared with the control group,the alcoholic liver disease group had 12 kinds of up-regulated proteins and 94 kinds of down-regulated proteins.Among them,there were 2 kinds of up-regulated differential proteins related to lipid metabolism and 14 kinds of down-regulated differential proteins.The results of bioinformatics analysis showed that these proteins were primarily involved in biological processes such as lipid transport,regulation of lipase activity,fatty acid binding,and cholesterol metabolism in lipid metabolism and also had a close link to signal pathways related to lipid metabolism such as peroxisome proliferator-activated receptor signaling pathways,cholesterol metabolism,triglyceride metabolism,and regulation of lipolysis in adipocytes.Conclusion The 16 kinds of lipid metabolism-related differential proteins may be the key proteins in the pathogenesis of alcoholic liver disease.

关 键 词：酒精性肝硬化 过氧化物酶体增殖物激活受体 胆固醇代谢 酒精性肝病 差异蛋白 脂代谢 脂肪酶活性 串联质谱 

分 类 号：R575.5[医药卫生—消化系统]