Study On The Biomarkers Of Pathogenesis Of Stasis-heat In Acute Intracerebral Hemorrhage Based On The Plasma Metabonomics

Purpose To screen and evaluate plasma differential metabolites in the acute phase of ICH and ICH of the pathogenesis of stasis-heat based on the plasma differential metabonomics,and to search for potential biomarkers for diagnosis of them respectively.Methods According to the rating scale of Stasis-heat in Intracerebral Hemorrhage in Traditional Chinese Medicine,80 clinical ICH patients including 40 patients with clinical stasis-heat(YP)and 40 patients with clinical nonstasis-heat(FP)were collected,adding 40 healthy controls(JP).Plasma differential metabolites were detected by liquid chromatography-mass spectrometry(LC-MS)between disease group and healthy group,as well as the stasis-heat group,the nonstasis-heat group and the healthy group were compared with each other.Principal component analysis(PCA),partial least square discriminant analysis(PLS-DA)and orthogonal partial least square discriminant analysis(OPLS-DA)were used to analyze the metabonomics data multidimensional statistical analysis to screen the potential biomarkers in Acute Intracerebral Hemorrhage and its pathogenesis of stasis-heat.Results(1)Twenty-two plasma differential metabolites were detected in the disease group/healthy group,of which 2-?-dihydroxychalcone,bezafibrate,progesterone,SP600125,isofenphos-methyl,biliverdin,6-methoxyquinoline,ergothioneine were up-regulated,among them,the contents of SP600125,bezafibrate,isofenphos-methyl,and ergothioneine were particularly significant.Pentalenic acid,ilicic acid,dl-lanthionine,1,7-dimethylxanthine,oleoyl ethanolamide,ergonovine were down-regulated,especially the reduction in oleoyl ethanolamide was the most significant.The pathways involved were steroid hormone biosynthesis,galactose metabolism,histidine metabolism,fructose and mannose metabolism,porphyrin and chlorophyll metabolism.Eight metabolites with ROC curve were greater than 0.9,which SP600125,isofenphos-methyl,pentalenic acid,ilicic acid,resorcinol,dl-lanthionine,ergothioneine,oleoyl ethanolamide.These plasma differential metabolites were each closely related to vascular change,inflammation,apoptosis,oxidative stress,or bacterial infections.(2)Twenty-seven differential metabolites were detected in the YP/JP group,twenty-three differential metabolites were detected in the FP/JP group.Among them,19-hydroxy-17-oxoandrost-5-en-3-?-yl sulfate,marmesin,tubercidin,isofenphos-methyl,10-deoxymethynolide,SP600125,progesterone and ergothioneine were all up-regulated and the content of YP/JP group increased even more,the same common up-regulation of prunin 6-o-gallate,biliverdin,6-methoxyquinoline and 2-?-dihydroxychalcone were more significant in the FP/JP group;resorcinol,ergonovine,methyl jasmonate,ilicic acid and 1,7-dimethylxanthine were all down-regulated and the contents of them decreased more significantly in YP/JP group,at the same time,dl-2-amino-3-phosphonopropionic acid,oleoyl ethanolamide and pentalenic acid were also down-regulated and the contents reduced more significantly in the FP/JP group.In addition,up-regulated metabolites only appeared in YP/JP group were avenanthramide E,pristimerol,and chebulic acid,and down-regulated metabolites were D-pipecolinic acid,?-CEHC,1,2,3,5-tetrachloro-4-methoxybenzene and pyrilamine;Differential metabolites only appeared in FP/JP group all down-regulated,including 2,5-dimethylbenzaldehyde,epimedokoreanin A and 2-deoxyglucose.(3)Fourteen differential metabolites were detected in the FP/YP,except for resorcinol,all other metabolites were down-regulated,with propanoic acid,dTDP-4-dehydro-6-deoxy-?-D-glucose,and triglyceride being the most obvious.Nine pathways involved includes histidine metabolism,ubiquinone and other terpenoid-quinone biosynthesis,galactose metabolism,steroid hormone biosynthesis,valine,leucine and isoleucine degradation,arginine and proline metabolism.ROC curve area of the combination of cortisone 21-Acetate,methyl reserpate and triglyceride was 0.91.Conclusion SP 600125,oleoyl ethanolamide,and ergothioneine can be potential biomarkers for ICH,and their combination can be used for the early diagnosis.Cortisone 21-Acetate,methyl reserpate and triglyceride can be considered as a set of biomarkers in the pathogenesis of stasis-heat in Acute Intracerebral Hemorrhage,which can help the follow-up clinical monitoring and provide the basis for the pathogenesis of stasis-heat.