Proteomic Of Inflammatory Factors In The Plasma Of Elderly Patients With Postoperative Delirium After General Anesthesia

Background:Postoperative delirium(POD)is a common,life-threatening,and usually preventable clinical syndrome in the elderly that is characterized by acute attention and cognitive impairment.It typically occurs on postoperative days 1 to 3.The exact etiology of POD is unknown,but it is generally believed to be associated with neuroinflammation,β-amyloid(Aβ)formation,and cholinergic neurotransmitter dysregulation.The study of possible biomarkers of delirium may identify patients at risk,which may contribute to the understanding of the pathophysiology of postoperative delirium and lead to the development of new preventive and therapeutic tools.However,existing studies have shown that many markers are not specific enough to predict the risk of delirium and to diagnose it,and there is an urgent need to explore novel biomarkers.Proteomics analysis can detect nearly 100 proteins at once in a very small number of samples,which is relevant for identifying new predictive and diagnostic indicators related to POD pathology and developing potential therapeutic targets.This experiment uses proteomic techniques to detect inflammatory factors and explore the relationship between neuroinflammation and delirium.Methods:This prospective cohort study included a total of 23 patients(12 delirious patients and 11 non-delirious patients),aged 75～88 years,weighing 45～80 kg,with ASA classification Ⅱ-III,who underwent general anesthesia for major elective abdominal surgery at Henan Provincial People’s Hospital from January 2022 to August 2022.And 5 ml of venous blood from the patient’s elbow or central vein was taken before anesthesia(T0),24 h postoperatively(T1),48 h postoperatively(T2),and 72 h postoperatively(T3),respectively.Delirium assessment using the 3D-CAM or CAM-ICU scale and DRS score were performed twice in one day,at 9-11 a.m.and 17-19 p.m.,from postoperative day 1 to postoperative day 5.In this experiment,92 inflammatory proteins were detected using the Olink inflammation panel.The Olink Proteome relies on its core protein assay patent,Proximity Extension Assay(PEA),to break through the limitations of sensitivity,low specificity,limited dynamic range,massive sample consumption and low-through-put in traditional proteomics assays,which means it can accurately detect more than 3,000 proteins in 1～6 μL samples.We collect blood samples of 12 delirium patients and 11 non-delirium patients at T0、T1、T2、T3.Blood samples were obtained and immediately sent to the laboratory for centrifugation,stored at-80°C,and transported on dry ice for batch testing.Results:1.The analysis showed that a total of 15 inflammatory proteins were significantly differentially expressed between the delirium and non-delirium groups at four time points:30 min preoperatively(T0),1day postoperatively(T1),2 days postoperatively(T2),and 3 days postoperatively(T3).Preoperative differential factor:IL-12B;differential factor on postoperative day 1: CCL-20 and MMP-10;differential factor on postoperative day 2: AXIN1,LAP TGF-beta,STAMBP,CASP-8,IL-18,SIRT2,CD244,MCP-2,IL-7 and ST1A1;differential factor on postoperative day 3: CST5 and 4E-BP-1.2.Compared to the non-delirium group,the concentration of IL-12 B was lower in the delirium group.3.Compared to the non-delirium group,CCL-20 and MMP-10 were higher in the delirium group on the first postoperative day.According to ROC analysis of CCL-20 and MMP-10,CCL-20(AUC=0.777P=0.028)and MMP-10(AUC=0.760 P=0.039)could be used as predictors of delirium in the early postoperative period(first day)and had certain diagnostic value for POD.4.AXIN1,LAP TGF-beta,STAMBP,CASP-8,IL-18,SIRT2,CD244,MCP-2,IL-7 and ST1A1 were lower in the delirium group comparing to the non-delirium group on the second postoperative day;AXIN1and SIRT2 decreased with POD.5.Compared to the non-delirium group,CST5 and 4E-BP1 were lower in the delirium group on the third postoperative day.6.In GO enrichment,immune response was associated with delirium to a higher extent;delirium histones were enriched in more genes in extracellular space and extracellular region pathways.Conclusion:Both CCL-20 and MMP-10 are associated with neuroinflammation,and combined with the experimental results in this study,CCL-20 and MMP-10 were considered as predictors of delirium in the early postoperative period(first day)and have some diagnostic value for POD.