Screening Of Lipid Biomarkers For Delayed Neurocognitive Recovery Based On Lipidomics

ObjectiveIn this study,pseudotargeted lipidomics method based on ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS)was used to analyze the differential expressed lipids of delayed neurocognitive recovery(DNR)patients undergoing non-cardiac surgery with general anesthesia.The aim is to find potential lipid biomarkers for DNR.MethodsPatients,aged over 65 years old,who was scheduled to undergo elective non-cardiac surgery,and score of the mini mental state examination(MMSE)less than 23 points before surgery.All patients were undergone general anesthesia by endotracheal intubation.Cognitive function was assessed by the Montreal Cognitive Assessment(Mo CA)1 day before and 7 days after surgery or before discharge.Patients,a decrease of greater than or equal to 2 points on the Mo CA from preoperative to 7 days after surgery or before discharge,was happened DNR.Fasting venous blood was collected before surgery and a plasma sample bank was established for analysis.Plasma samples of the two groups were analyzed by pseudotargeted lipidomics method based on UHPLC-MS.Automatic batch processing such as peak extraction,peak alignment,peak identification,peak area integral and so on were performed using pseudotargeted lipidomics method based on UHPLC-MS.Finally,the derived qualitative and quantitative form was quantitatively analyzed by response factor method.Multivariate statistical analysis include principal components analysis(PCA),partial least squares discriminant analysis,(PLS-DA),Orthogonal partial least squares discriminant analysis(OPLS-DA).Univariate analysis include T test and fold change analysis.The different metabolites between two groups were screened by multivariate statistical analysis and univariate analysis.Significance of statistically was set at variable important in projection(VIP)of OPLS-DA>1 and P of T test < 0.05.Statistical software SPSS26.0 was used for data analysis of general characteristics and cognitive assessment scores.Results1.In a total of 77 patients who underwent elective non-cardiac surgery,20 patients were judged to have a DNR,the incidence of DNR was 26%.Finally,20 patients who undergoing non-cardiac surgery were judged to have DNR,and the incidence of DNR was 26%.Meanwhile,20 matched non-DNR patients were selected based on the type of surgery,age,sex,and body mass index.There was no statistical significance in age,gender,height,body weight and body mass index between the two groups(P>0.05).There was significant difference in the years of education,preoperative MMSE scores preoperative MOCA score and postoperative MOCA score between the two groups(P>0.05).2.PLS-DA model and OPLS-DA model could distinguish plasma samples from DNR group and non-DNR group,and OPLS-DA model had not been fitted.3.A total of 771 lipids were detected in the DNR and non-DNR groups,including388 glycerophospholipids(50%),200 glycerolipids(26%),107 sphingolipids(14%),59 fatty acyls(8%)and 17 sterol lipids(2%),respectively.4.There are 12 significant differential lipids in plasma between the DNR group and the non-DNR group,which are PC(18:0/18:1),PC(18:0/20:3),PC(16:0/16:1),PC(18:0/18:3),LPC(16:1),LPC(18:3),DAG(16:0/16:0),DAG(16:0/18:0),DAG(18:0/18:0),MAG(16:0),CE(22:1),SM(d18:1/24:2)(VIP>1,P<0.05).Compared with non-DNR group,11 significantly different lipids were down-regulated in DNR group(FC<1).SM(D18:1/24:2)were up-regulated in DNR group(FC>1).Conclusionwe found that there were changes in lipid metabolism in DNR patients,mainly changes in glycerophospholipids and glycerolipids metabolism by pseudotargeted lipidomics method based on UHPLC-MS.PC(18:0/18:1),PC(18:0/20:3),PC(16:0/16:1),PC(18:0/18:3),LPC(16:1),LPC(18:3),DAG(16:0/16:0),DAG(16:0/18:0),DAG(18:0/18:0),MAG(16:0),CE(22:1),SM(d18:1/24:2)may be potential lipid biomarkers of DNR.