Protective Effect Of Pituitary Adenylate Cyclase Activating Polypeptide On Focal Cerebral Ischemia Reperfusion Injury In Rats

Objective To investigate the protective effect of pituitary adenylate cyclase activating polypeptide(PACAP) on focal cerebral ischemia reperfusion injury in rats and its probable mechanism in order to provide the experiment support for the clinical therapy of ischemic cerebrovascular disease.Mothods All rats were randomly divided into sham group,model group and PACAP38 treatment group.PACAP38 was administered after a 2-hour transient MCAO using a filament mode as an intravenous bolus(20 nmol·kg-1) followed by an intravenous infusion using a micro-osmotic pump at a rate of 160 pmol per hour.Brain water content(BWC) was measured by dry-wet weighting method.The expression of AQP4 protein and mRNA was assessed by immunocytochemistry and reverse transcriptase polymerase chain reaction(RT-PCR) technique,the activity of superoxide dismutase(SOD),the content of malondialdehyde(MDA) and the content of nitrogen monoxidum(NO) of the brain tissue were determined.Results1.Compared with sham group,BWC increased obviously after MCAO 6h in model group and PACAP38 treatment group.BWC in PACAP38 treatment group was remarkably less than the model group at same time point.2.Compared with sham group,Expression of AQP4 protein increased obviously after MCAO 6h in model group and PACAP38 treatment group.Expression of AQP4 protein in penumbra area in PACAP38 treatment group was remarkably less than the model group at same time point.3.Compared with sham group,Expression of AQP4 mRNA increased obviously after MCAO 6h in model group and PACAP38 treatment group.Expression of AQP4 mRNA in penumbra area in PACAP38 treatment group was remarkably less than the model group at same time point.4.Compared with sham group,The activity of SOD decreased obviously after MCAO 6h in model group and PACAP38 treatment group.The activity of SOD in PACAP38 treatment group was remarkably high than the model group at same time point.5.Compared with sham group,The content of MDA increased obviously after MCAO 6h in model group and PACAP38 treatment group.The content of MDA in PACAP38 treatment group was remarkably less than the model group at same time point.6.Compared with sham group,The content of NO increased obviously after MCAO 6h in model group and PACAP38 treatment group.The content of MDA in PACAP38 treatment group was remarkably less than the model group at same time point.Conclusions PACAP have obvious protective effect on ischemical reperfusion injury of focal brain tissue in rat and its probable mechanism is through lessening Expression of AQP4 protein and mRNA,cleaning free radicals and attenuating cerebral lipid peroxidation.