The Role Of Cyclooxygenase-1 In Cerebral Ischemia Reperfusion Injury

Objective:In this study,we investigated the relationship between COX1 and PGD2/DP1 receptors in a transient middle cerebral artery occlusion（t MCAO）mouse model,and the role of COX1 in inflammation of cerebral ischemia/reperfusion injury.Methods:C57BL/6 mice and Cyclooxygenase1（COX1）gene knockout mice were treated with t MCAO for 60min and then reperfusion.The mice were divided into COX1^+/+Sham group,COX1^-/-Sham group,COX1^+/+MCAO 24h group and COX1^-/-MCAO 24h group.Neurological function score was performed 24 hours after operation,and TTC staining results were used to calculate the postoperative cerebral infarction volume.The survival rate of neurons and the activation of microglia were observed by immunohistochemical staining.Western blot was used to detect COX1 and nucleotide-binding oligomerization domain-like receptor protein 3.NLRP3,interleukin-1β（IL-1β）,and cysteinyl aspartate specific proteinase（caspase-1）.The content of prostaglandin D2（PGD2）in each group was determined by mass spectrometry.The m RNA expression levels of COX1,DP1,NLRP3 and IL-1βwere detected by fluorescence quantitative PCR.Results:1.The cerebral infarction volume of COX1^-/-rats was increased,and the neurological damage was aggravated.2.In COX1^-/-mice,the survival rate of neurons in cerebral cortex and hippocampus CA1 region decreased,and the activation of microglia cells increased.3.PGD2 production and DP1 m RNA levels were significantly decreased in COX1^-/-mice.4.The m RNA and protein expression levels of NLRP3and shear IL-1βwere significantly increased in COX1^-/-mice,and the protein expression levels of shear Caspase-1 were significantly increased.Conclusion:MCAO24h after COX1 gene knockout,the infarct volume increased,the nerve function injury increased,the neuronal survival rate decreased,the microglial cell activation increased,the expression of PGD2 and DP1decreased,and the NLRP3,shearing caspase-1 and the precursor IL-1βincreased.