Yang Zhiyong, Qiu Guosheng, Li Xing, Li Sijie, Yu Chaoming, Qin Yuanhan
Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Transl Pediatr. 2022 Jan;11(1):58-72. doi: 10.21037/tp-21-559.
Brain death (BD) is a catastrophic physiological outcome that can occur in individuals with terminal illness and can adversely affect the graft quality after donation of their organs. As BD has no specific symptoms, it can be difficult to diagnose in a timely manner. The present study was designed to investigate the serum protein expression profiles of children affected by BD in an effort to define diagnostic biomarkers for this condition.
Blood samples were collected from 8 patients with BD and 8 healthy controls during the same time period. Tandem mass tags and mass spectrometry were used to conduct a proteomic analysis of serum extracted from the samples. The potential regulatory roles of the top 5 upregulated and downregulated proteins identified through the analysis were then explored using bioinformatics analyses and a review of the related literature.
The top 5 upregulated proteins in the serum samples from patients with BD were lipopolysaccharide-binding protein (LBP), α1-acid glycoprotein (α1-AGP), α1-antichymotrypsin (α1-ACT), leucine-rich α1-glycoprotein (LRG1), and lactate dehydrogenase B heavy chain (LDHB), and the 5 most downregulated proteins in these samples were actin-binding protein 2 (transgelin-2), platelet basic protein (PBP), tropomyosin α4 chain (TPM4), tropomyosin α3 chain (TPM3), and peptidase inhibitor 16 (PI16). Literature searches indicated that several of the identified proteins influence the pathogeneses of various diseases, with LBP, α1-AGP, α1-ACT, LRG1, transgelin-2, and PBP all being related to inflammatory activity.
Through a proteomics-based analysis, several differentially expressed proteins were identified in patients with BD relative to healthy controls. Most of these proteins are associated with inflammatory responses that have the potential to persist after the occurrence of BD. Further clinical work is needed to clarify the functional roles of the identified proteins.
脑死亡(BD)是一种灾难性的生理结局,可发生于终末期疾病患者,并且会对其器官捐献后的移植物质量产生不利影响。由于脑死亡没有特定症状,可能难以及时诊断。本研究旨在调查受脑死亡影响儿童的血清蛋白表达谱,以确定该病症的诊断生物标志物。
在同一时期从8例脑死亡患者和8名健康对照者采集血样。采用串联质谱标签和质谱法对从样本中提取的血清进行蛋白质组学分析。然后利用生物信息学分析和相关文献综述,探讨通过分析确定的上调和下调程度最高的5种蛋白质的潜在调节作用。
脑死亡患者血清样本中上调程度最高的5种蛋白质是脂多糖结合蛋白(LBP)、α1-酸性糖蛋白(α1-AGP)、α1-抗糜蛋白酶(α1-ACT)、富含亮氨酸的α1-糖蛋白(LRG1)和乳酸脱氢酶B重链(LDHB),这些样本中下调程度最高的5种蛋白质是肌动蛋白结合蛋白2(转胶蛋白-2)、血小板碱性蛋白(PBP)、原肌球蛋白α4链(TPM4)、原肌球蛋白α3链(TPM3)和肽酶抑制剂16(PI16)。文献检索表明,几种已鉴定的蛋白质影响多种疾病的发病机制,LBP、α1-AGP、α1-ACT、LRG1、转胶蛋白-2和PBP均与炎症活动有关。
通过基于蛋白质组学的分析,相对于健康对照者,在脑死亡患者中鉴定出几种差异表达的蛋白质。这些蛋白质中的大多数与炎症反应相关,炎症反应在脑死亡发生后可能持续存在。需要进一步的临床工作来阐明已鉴定蛋白质的功能作用。