Dissecting Lipid-induced Inflammatory Molecular Pathways During Brain Recovery Following Middle Cerebral Artery Occlusion In Mice

Stroke has become one of the most serious diseases that threaten human life and is seriously threatening the survival,health and quality of life of residents.At present,there is little known about the molecular mechanism of stroke and stroke therapy can only be performed in a weak way through the bolt.As a branch of metabonomics,lipidomics has been increasingly used in the field of biomedical research over the past years to diagnose biomarkers of related diseases and reveal the molecular mechanism of the disease.This reasearch aims to explore the changes of endogenous neurolipids induced by stroke using lipidomics technology,find the key lipid molecules in the recovery phase of stroke,explore the molecular mechanism of post-stroke neuroinflammation,and discover the lipid biomarkers that protect nerve cells.To develop new methods for effective treatment of stroke.In this dissertation,mouse MCAO model of cerebral apoplexy disease was used to study the changes of different lipids in the cerebral cortex of mice after cerebral ischemia/reperfusion injury using a high-sensitivity UPLC-MS analysis platform and establish a group of metabolic brain lipid profiles.The establishment of PCA model and OPLS-DA model was used to analyze 578 lipid molecules in 41 lipid samples collected from 1,3,7,14 and 28 days after cerebral ischemia/reperfusion in mice and sham operation group.In combination with the OPS-DA model with VIP > 1 and the t-test,p < 0.05,a total of 84 major lipid compounds were screened out,and 84 changes in lipids during recovery and MCAO behaviors were statistically analyzed.Seven potential biomarkers were obtained: PC(20:4/22:6),PC(16:0/18:2),PC(16:0/16:0),LPC(16:0),PG(18:1/20:4),PE(16:0p/16:1)and Cer(d18:2/18:0).Among them,PC(16:0/16:0)and LPC(16:0)lipid molecules showed the most significant changes during the long time recovery period,and PC(16:0/16:0)produced LPC(16:0)under the action of phospholipase A2.By studying the relationship between PC(16:0/16:0)with LPC(16:0)and microglia activation,we found that neither PC(16:0/16:0)nor LPC(16:0)could make microglia activate and secret inflammatory cytokines.By establishing LPS-induced microglia activation and secretion of TNF-? and IL-1? inflammation models.We found that PC(16:0/16:0)can significantly reduce LPS-induced microglia cells secreted TNF-?,IL-1?.The PC(16:0/16:0)molecule as a potential neuroprotective agent has important implications for the recovery of post-stroke neuroinflammation.