| ObjectiveTo investigate the changes of serum kynurenine pathway(KP)metabolite levels in patients with aneurysmal subarachnoid hemorrhage(aSAH)and its correlation with acute brain edema.MethodsThe study group included 32 patients with aSAH,and the control group included 28 healthy volunteers.aSAH patients completed the cranial CT scan and the first venous blood collection within 24 hours of admission,and continuous venous blood collection was performed on 2～4 and 7 days.A single venous blood was collected during the physical examination of healthy volunteers.Used the Subarachnoid Hemorrhage Early Brain Edema Score(SEBES)to assess the degree of brain edema.High performance liquid chromatography(HPLC)was used to determine serum tryptophan(TRP),kynurenine(KYN)and kynurenic acid(KYNA)concentrations,and gas chromatography-mass spectrometry(GC/MS)to determine serum quinolinic acid(QA)concentration.SPSS 22.0 and Graph Pad Prism8 software were used for statistical analysis and statistical drawing.The measurement data is represented by the median and interquartile range M(P25-P75).The TRP,KYN,KYNA,and QA data were logarithmically transformed and obey the normal distribution.The comparison between multiple groups of the study group at each time point and the control group was performed by one-way analysis of variance(One-way ANOVA).The each time point group in study group is compared pairwise with the control group using LSD-t test.The data KYNA/KYN,QA/KYN,QA/KYNA of the study group at each time point is non-normal.The comparison between multiple groups was performed by Kruskal-Wallis rank sum test.The study group 1d was used as the control,other time point groups in the study group were compared pairwise with it using Bonferroni correction test.Correlation analysis between serum TRP,KYN,KYNA,QA levels and SEBES in study group was conducted using Spearman rank correlation analysis.P<0.05 considered the difference to be statistically significant.Result1.Changes in serum KP metabolite levels in patients with aSAHCompared with the control group,the serum concentration of TRP in the study group decreased from day 1 to day 4,and the decrease of TRP concentration at day 2,day 3 and day 4 was statistically significant(P<0.05).The concentration of TRP increased from the previous level at day 7(P>0.05).In the study group,the serum KYN concentration fluctuated slightly from day 1 to day 3(P>0.05),and then increased at day 4 and day 7(P<0.05).The serum KYNA concentration in the study group increased from day 1 to day4,and increased at day 3 and day 4 with statistical significance(P<0.05).The serum KYNA concentration at day 7 was slightly lower than that at day 4,but was still significantly higher than that in the control group(P<0.05).In contrast to KYNA,the serum QA concentration in the study group increased significantly from day 2(P<0.05),reached the peak at day 4(P < 0.001),and remained at a high level at day 7(P < 0.001).2.Changes in the ratio of serum KP metabolites in patients with aSAHWhile the ratio at day 1 in the study group taken as control,The KYNA/KYN ratio was significantly increased at day 2 and day 3(P < 0.001).The KYNA/KYN ratio began to decline at day 4(P>0.05),and was significantly decreased at day 7(P < 0.05)compared with the control.The other metabolic branch,KYN-QA,showed a similar trend.The QA/KYN ratio was significantly increased at day 2 and day 3(P < 0.001),then decreased at day 4 and day 7(P > 0.05).Further comparison of the two downstream metabolites of KYN showed that the QA/KYNA ratio in the study group was significantly higher at day 2 than at day 1(P < 0.05).The QA/KYNA ratio at day 3,day 4 and day 7fluctuated steadily,and increased slightly compared with day 1,but there was no statistical difference(P > 0.05).3.Correlation between serum KP metabolite levels and brain edema degree in aSAH patientsThere was no significant correlation between the concentration of TRP,KYN,KYNA and SEBES on the first day of the study group(r=-0.11,P = 0.533;r=0.28,P=0.126;R=0.14,P=0.448),QA concentration was positively correlated with SEBES(r=0.39,P=0.028).ConclusionThe metabolites of kynurenine pathway changed significantly in patients with acute aSAH.With the passage of time,the concentration of serum TRP decreased significantly,while the concentrations of KYN,KYNA and QA increased significantly.Compared with the production of KYNA,the increase of QA is more significant,suggesting that KP metabolism is mainly progressing to TRP-KYN-QA metabolic pathway.Further analysis found that the QA level was correlated with the degree of brain edema.Therefore,it is reasonable to believe that QA,as a metabolite in KP,can indirectly reflect the degree of brain edema in the acute stage after aSAH,and can provide a reliable predictive index for the early intervention of brain edema. |
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