Proteomics-metabolomics Integration Strategy For Exploring The Mechanism Of Vascular Depression In Mice

Depression has recently become the world's most important mental health problem,which brought a heavy burden on society.As a typical subtype of depression,vascular depression(VD)is caused by vascular disease or cerebrovascular risk factors.Except to the typical depression symptoms like extremely low emotion,insomnia and dreaminess,loss of appetite,patients with VD usually suffer from executive dysfunction,psychomotor retardation,thinking slow,significantly weaken in comprehension and may lead to suicide.In recent years,vascular depression takes a great increasing proportion in patients with major depression,which seriously influences not only the quality of patients' life,but also their works,families and society.Unfortunately,it is not optimistic for its current situation? Since its severe dysfunction,complex causes and vague clinical diagnostic indicators,the basic research of vascular depression is relatively weak and there is still no comprehensive explanation of the mechanism,which results in poor treatment reaction,really long course and easy to relapse.In order to accumulate the basic explorations of vascular depression and make some contributions to mechanism research,clinical diagnostic biomarkers discovery and medicine development,this study attempts to establish a protein-metabolite overall regulatory network for vascular depression mouse model based on the integration of proteomics and metabonomics which both rely on LC-MS platform technology to explain the effect and disturbance which vascular depression bring to body comprehensively.In order to achieve the above purpose,we firstly established a vascular depression mice model caused by global cerebral ischemic(GCI)by using bilateral common carotid arteries ligation.Then we developed an approach by combining metabonomics and iTRAQ-labeled proteomics to analyze the hippocampus of vascular depression mice.As a result,44 differentially expressed metabolites and 304 differentially expressed proteins were screened in this process.Subsequently,with the help of Ingenuity Pathway Analysis software,we analyzed the association and integration of differential metabolites and proteins to construct a protein-metabolite overall regulatory network.After that,LC-MS/MS,western blot and Rt-Q-PCR were applied for the quantitative analysis of bimolecular involved in the focused pathways in bioinformatics analysis.The results suggest that changes were happened in the regulation of neural plasticity,transportation and function of excitatory neurotransmitter,imbalance of neural cell proliferation and apoptosis and disorder of amino acid,lipid and energy metabolism.These perturbed pathways include lots of differential proteins and their downstream metabolites screened in our omics analysis work,and the association between different levels of bimolecular will provide a more targeted and credible direction for further study of the pathogenesis of vascular depression.Additionally,these altered bimolecular will also be potential therapeutic targets or biomarkers for vascular depression.Therefore,the combination between proteomics and metabonomics presented in this paper which can focus on research directions and screen potential targets and biomarkers is a good way to narrow the scope of deeper research and provide a more accurate,more credible,more pioneering potential research direction,especially for some diseases with poor basic research and accumulation,such as vascular depression.Simultaneously,it is also helpful for the further development of drug discovery,clinical diagnosis and treatment of vascular depression.