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.Methods In this paper, the models of focal cerebral ischemia reperfusion in rats were established with suture-occluded method to simulate the middle cerebral artery ischemia reperfusion injury in clinic. The treatment groups were given three different dose PACAP (PACAP 10-11 mol,PACAP 10-10 mol and PACAP 10-9 mol) in 15minutes be-fore cerebral ischemia. PACAPs were infused into lateral cerebral ventricle by microin-jector. The volume of the cerebral infarction, water content of brain, the activity of su-peroxide dismutase (SOD), the content of malondialdehyde (MDA) and the content of nitrogen monoxidum (NO) of the brain tissue were determined. The amount of survival neurons in ischemia reperfusion areas was counted.Results1. The injuring brain tissue has obvious infarction in NS group. In PACAP treatment groups, the infarction volume of brain is lower compared with NS group. In PACAP treatment groups, the infarction volume of brain is lessening in middle and high dose group compared with low dose group (P<0.05). There is no significant differ-ences between the high and middle dose groups (P>0.05).2. Compared with the PACAP treatment groups, the edema is aggravated at injuring brain tissue in the NS group which has been reperfused 24 hours after cerebral ischemia 2 hours. In PACAP treatment groups, water content of brain is lessening in middle and high dose group compared with low dose group (P<0.05). There is significant differences between the high and middle dose groups (P<0.05).3. The activity of SOD is decrease in NS group (P<0.05). In PACAP treatment groups, the activity of SOD is high in middle dose groups than low dose group (P<0.05). There is no significant differences between the high and low dose groups (P>0.05) and the high and middle dose groups (P>0.05).4. The content of MDA is higher in NS group than PACAP high and middle dose groups (P<0.05). It has no significant difference between low dose group and NS group (P>0.05). In PACAP treatment groups, the content of MDA is lessening in middle and high dose group compared with low dose group (P< 0.05). There is no significant differences between the high and middle dose groups (P>0.05).5. The content of NO is higher in NS group than PACAP high and middle dose groups (P<0.05). It has no significant difference between low dose group and NS group (P>0.05). In PACAP treatment groups, The content of NO is lessening in middle and high dose group compared with low dose group (P< 0.05). There is no signifi-cant differences between the high and middle dose groups (P>0.05).6. The amount of survival neurons in ischemia reperfusion areas is lower in NS group than PACAP high and middle dose groups (P<0.05). It has no significant difference between low dose group and NS group (P>0.05). In PACAP treatment groups, The amount of survival neurons in ischemia reperfusion areas is lessening in low dose group compared with middle and high dose groups (P<0.05). There is no significant differences between the high and middle dose groups (P>0.05).Conclusions PACAP have obvious protective effect on ischemical reperfusion injury of focal brain tissue in rat and its probable mechanism is through lessening the infarc- tion volume of brain, the water content of brain, clear free radicals and attenuating cerebral lipid peroxidation.