Effect Of Indoleamine 2,3-dioxygenase Inhibitor On Cognitive Function And Its Mechanism In Chronic Cerebral Hypoperfusion Rats

Objective:By observing indoleamine 2,3-dioxygenase(IDO),tryptophan 2,3-dioxygenase(TDO)and blood dogs in the hippocampus of chronic cerebral hypoperfusion model rats Urine quinolinic acid(KYNA),quinolinic acid(QA)content and its content after using IDO inhibitors,to explore the protective effect of IDO inhibitors on the cognitive function of chronic cerebral hypoperfusion rats And its mechanism.Methods:39 male SD rats were randomly divided into a sham operation group,an operation group and an IDO inhibitor group,with 13 rats in each group.Among them,the operation group and the IDO inhibitor group used modified permanent common carotid artery ligation to make a chronic cerebral hypoperfusion rat model.The sham operation group did not ligate the common carotid artery during model preparation.The IDO inhibitor group was intragastrically administered with 1-MT suspension,and the other two groups were intragastrically administered with saline for 14 days.Morris water maze was used to detect changes in spatial learning and memory in rats.ELISA was used to detect blood KYNA and QA levels.RT-PCR was used to detect the expression levels of IDO and TDO mRNA in rat hippocampus.Western blot was used to detect rat IDO,TDO protein expression level.Results:(1)Morris water maze results: Compared with the sham operation group,the escape latency was prolonged on the first,second,and fifth days in the operation group;compared with the operation group,the escape latency was shorter on the first,second,fourth,and fifth days in the IDO inhibitor group,The percentage of platform quadrant swimming distance increased and behavioral performance improved significantly.(2)ELISA test results: There was no significant difference in blood KYNA content between the three groups of rats(P> 0.05);The expression levels of QA in the operation group,IDO inhibitor group,and sham operation group decreased in turn,and their expression levels were(915.27±52.74)pg/ml vs(784.90±37.65)pg/ml vs(670.20±28.05)pg/ml,There are statistical differences between the groups(P<0.05).(3)Detection results by RT-PCR technology: Compared with the sham operation group,the transcription level of the IDOmRNA in the hippocampus region of the operation group was significantly increased(P <0.05);compared with the operation group,the IDO and TDOmRNA in the hippocampus region of the IDO inhibitor group mRNA transcription level was significantly reduced(P <0.05).(4)Western blot detection results: Compared with the sham operation group,the expression of TDO in the hippocampal region of the IDO inhibitor group was reduced(P<0.05);compared with the operation group,the IDO and hippocampal region of the IDO inhibitor group were increased.The protein expression of TDO was significantly reduced(P <0.05).Conclusion:IDO inhibitors can significantly improve cognitive function in rats with chronic cerebral hypoperfusion,and its mechanism may be related to reducing the levels of blood QA and hippocampal IDO and TDO.