Identification of novel biomarkers and therapeutic target candidates for stasis-heat symptom pattern of acute intracerebral hemorrhage by quantitative plasma proteomics

OBJECTIVE:To explore the novel biomarkers and therapeutic target candidates related to the stasis-heat syndrome of acute intracerebral hemorrhage(AICH).METHODS:Applying an isobaric tagging for relative and absolute quantitation-(i TRAQ-)based quantitative proteomic approach,plasma samples from AICH patients with stasis-heat,and AICH patients with non-stasis-heat and healthy control subjects were collected and analyzed to distinguish differentially expressed proteins(DEPs)correlated to AICH with stasis-heat in this block design.The standard Western blot was applied to verify DEPs.Additionally,DEPs were analyzed via bioinformatic platforms and further approved via Ingenuity Pathway Analysis(IPA).RESULTS:A total of 26 DEPs were found among AICH with the stasis-heat,AICH with non-stasis-heat,and healthy control group.The seven DEPs compared with the non-stasis-heat group are closely related to the pathogenesis of stasis heat.These proteins showed three different protein expression patterns.The alpha-1-b glycoprotein(A1 BG)and copper-protein(CP)were upregulated in the stasis-heat group,but down-regulated in the non-stasis-heat group.Compared with the non-stasisheat group,the expression abundance of actinin,alpha 1(ACTN1),carbonic anhydrase I(CA1),peroxiredoxin 2(PRDX2),and vinculin(VCL)is higher in the stasis-heat group,while the CD44 is the opposite.These differences reflect that stasis-heat syndrome has more severe inflammatory immune response,coagulation disorders and damage.Bioinformatics analysis revealed that a wide variety of cellular and metabolic processes and some signaling pathways were involved in the pathophysiology of AICH with stasis-heat.AICH with stasis-heat syndrome showed more severe inflammatory reactions,tissue damage,and coagulation disorders than non-stasis heat syndrome.CONCLUSIONS:There are differences in the protein expression patterns between the stasis-heat syndrome and non-stasis-heat syndrome.These differences reflect that stasis-heat syndrome has more severe damage.CD44,CP,ACTN1,CA1,VCL,PRDX2,and A1 BG could be the potential biomarkers and therapeutic target candidates of the stasis-heat subtype.This study provides a reasonable explaination for Liangxue Tongyu decoction through anti-inflammatory and brain protection treatment.