Neuroprotective Effect For Cognitive And Mechanism Of Interleukin 1 Receptor Antagonist On Chronic Cerebral Hypoperfusion Rats

Objective:(1)To observe the effect of interleukin-l receptor antagonist(IL-1ra)on the learning and memory ability, IL-1β, IDO expression in hippocampal CA1 area and IDO activity on chronic cerebral hypoperfusion rats;(2)Investigating the neuroprotective effect for cognitive and mechanism of IL-1ra.Methods:A total of 36 healthy male SD rats( 170-200 g) were randomly divided into 3groups( n=12) :sham operation group,CCH group and IL-1ra group.Latter two group were induced by improved bilateral common carotid artery occlusion.After surgery, the rats in IL-1ra group were given intracerebroventricular injection of human recombinant IL-1ra(10μL/ day only).The sham operation group and the model group were injected with equal volume of normal saline.Morris water maze test was used to measure the learning and memory ability of rats. The positive expression levels of IDO and IL-1 in hippocampus CA1 area were detected by immunohistochemistry.ELASA method was used to detect the levels of kynurenine(KYN) and tryptophan(Trp)in the hippocampus of rats in each group.Results:(1) Morris water maze navigation experiment, training 4, 5 days, the rats in the model group escape latency time were significant higher than those in the sham operation group(P <0.05), and IL-1ra group rats on day 4 and 5 escape latency time less than those in the model group(P <0.05).Space exploration experiment: swimming speed difference was not statistically significant(P>0.05), showed that the operation and micro injection treatment did not affect the whole body movement ability. Compared with the sham operation group, the number of times of the model group crossing the platform and the residence time of target quadrant were significantly reduced(P<0.05). The time of the IL-1ra group crossing the platform and the residence time of the target quadrant were significantly increased(P<0.05).(2) Immunohistochemistry: compared with sham operation group, model group IL-1β,IDO positive expression was significantly increased(P<0.05). Compared with the model group, IL-1ra group IL-1β, the positive expression of IDO was significantly lower(P <0.05).(3) ELISA results: compared with sham operation group, the KYN/Trp ratio of model group was significantly decreased(P<0.05).Compared with the model group,the KYN/Trp ratio of IL-1ra group ratio was decreased significantly(P < 0.05).Conclusion:(1)The spatial learning and memory ability of CCH rats decreased and the expression of IL-1β, IDO and IDO activity was increased in hippocampus.(2)Human recombinant IL-1ra can improve the ability of learning and memory,reduce the expression of IL-1β, IDO and inhibit the activity of IDO.That may through the antineuritic damage and inhibition of the kynurenine pathway to play the role of cognitive protection.