Study On Mechanisms Of Auricular Point Comprehensive Therapy For Migraine Based On Proteomics/Metabolomics

Objective: The study explored the clinical efficacy of auricular acupoint comprehensive therapy in the treatment of clinical migraine patients.Using proteomics and metabonomics technology,we studied the molecular biological mechanism of auricular acupoint comprehensive therapy for migraine,searched for functional modules and key nodes at the level of protein and metabolic network,and further revealed the intervention mechanism of auricular acupoint comprehensive therapy for migraine.Methods: The study evaluated clinical effectiveness of auricular acupoint comprehensive therapy for migraine.Proteomic TMT(Tandem Mass Tag)technique and metabolomic UPLC-Q-Exactive MS/MS technique were used to detect the plasma of migraine patients before and after treatment.Enzyme-linked immunosorbent assay(ELISA)was used to verify the protein.Results: 1.Auricular acupoint comprehensive therapy can significantly reduce the migraine headache score and VAS value of migraine patients.The total clinical effective rate is 93.33%.After 8 weeks follow-up,the curative effect is stable and the recurrence rate is low.2.Proteomics techniques identified 14 up-regulated proteins such as IL-6R,PF4,SOD1 in migraine patients as compared with normal subjects,11down-regulated proteins such as SASH1,IGKV2-29 and SELL,the enriched pathway includes chemokine signaling pathway and cytokine-cytokine receptor interaction pathway;Auricular point comprehensive therapy gets 2up-regulated proteins such as SASH1,ZBED1,12 down-regulated proteins suchas IL-6R,YWHAE and NME2,the enriched pathway includes human cytomegalovirus infection pathway and PI3K-AKT signaling pathway.3.Metabonomics Technology identified 37 up-regulated metabolites such as L-lysine,7-methylxanthine and 3-methylxanthin,19 down-regulated metabolites such as dopamine,tyramine and glutarate in migraine patients compared with normal people,and enriched 11 pathways such as linoleic acid metabolism and caffeine metabolism;Auricular point comprehensive therapy gets 10 up-regulated metabolites such as L-aspartic acid,L-tyrosine and heptanedioic acid,16 down-regulated metabolites such as L-lysine,7-methylxanthine and 3-methylxanthine,and enriched in 8 metabolic pathways su ch as lys in e degr a da ti on an d ph eny l ala n ine me tabo lism.Conclusions: Auricular point comprehensive therapy for migraine had definite clinical effect and stable long-term effect,which is worthy of popularization and application.Its mechanism is related to the involvement of multiple proteins such as YWHAE,SASH1,IL-6R and metabolites such as tyrosine,phenylalanine and L-lysine.It involves the changes of human giant cell infection pathway,PI3K-AKT signaling pathway,arachidonic acid metabolism,caffeine metabolism and other signaling pathways.This study helped us find the right entry point of the mechanism of auricular point comprehensive therapy in the treatment of migraine in the future study.