Proteomics Of Xuefu Zhuyu Decoction In The Treatment Of Cognitive Impairment In Traumatic Brain Injury

Objectives: The study aimed to combine proteomics and network pharmacology to reveal the molecular mechanism of xuefu zhuyu decoction(XFZYD)improving cognitive impairment after traumatic brain injury(TBI).Methods:(1)The sprague-dawley(SD)rats were randomly divided into sham operation group(Sham),model group(TBI)and xuefu zhuyu decoction group(XFZYD)to establish a controlled cortical impact(CCI)rat model.And the rats were given the same volume of distilled water or XFZYD for 14 days.(2)The neurological deficits were assessed by modified neurological severity score(m NSS).Spatial learning and memory abilities were evaluated by the Morris water maze.Hematoxylineosin staining(HE)and Nissl staining were employed for observe the pathological changes of brain tissue.Golgi staining was employed for observe the neuronal dendritic structural changes.(3)The quantitative proteomics based on Tandem Mass Tag-based(TMT)detected the protein expression in rat hippocampus,and screened out differentially expressed proteins(DEPs).(4)Using network pharmacology to obtain potential targets of XFZYD for the treatment of cognitive disorders after TBI.The bioinformatics analysis was carried out with DEPs and potential targets to obtain the potential molecular mechanism of XFZYD improving cognitive impairment after TBI.Finally,DEPs were verified by western blot(WB).Results:(1)XFZYD could alleviate neurological deficits in TBI rats,enhance the plasticity of neuronal synaptic structure,and improve cognitive disorders.(2)16 DEPs were screened by proteomics,239 potential targets were obtained by network pharmacology,and 8 DEPs were found to interact with potential targets by protein interaction analysis.(3)Bioinformatics analysis found that the improvement of cognitive impairment after TBI by XFZYD may be related to PI3K-Akt signaling pathway and MAPK signaling pathway.(4)ALYREF,ENPP2,and S100A4 were validated,and the results were consistent with proteomics.Conclusions: XFZYD may improve cognitive impairment after TBI through multiple targets,such as ALYREF,S100A4,ENPP2,and multiple pathways including PI3K-Akt signaling pathway and MAPK signaling pathway.