Effect Of Indoleamine2,3-dioxygenase Inhibitor On Cognitive Impairment In Rats With Chronic Cerebral Hypoperfusion

Objective:Use IDO inhibitors after chronic cerebral hypoperfusion rats the change of the concentration of serum KYN and KYNA, the expressions of IFN‐γ, TNF‐α, and cognitive impairment due to chronic cerebral hypoperfusion behavior improvement.Method:1. Morris water maze test using IDO inhibitors after 2VO rat spatial learning and memory ability.2. Expressions of IFN‐γ, TNF-α in hippocampal CA1 area were detected by immunohisto‐chemistry.3. High-performance liquid chromatography with fluorescence detection(HPLC-FLD)assay to detect Kynurenine(KYN), Kynurenic acid(KYNA) content.Results:1. The water maze behavior test results: 4, 5 days IDO inhibitor group rat escape latent period 23.41±29.75, 21.45±29.91, are shorter than in the control group 49.37±10.47,37.22±28.39, the difference was statistically significant(P<0.05), were higher than in control group 17.12±12.2, 10.90±10.14, there was no statistically significant difference(P>0.05); IDO inhibitor group platform quadrant swimming distance percentage0.54±0.044, higher than that of control group 0.29±0.063, the difference was statistically significant(P<0.05); Were lower than control group 0.56±0.028, there was no statistically significant difference(P>0.05);2. The high performance liquid chromatography(HPLC) with fluorescence detection results: group of serum KYN and KYNA IDO inhibitors respectively 1.69±0.936,25.66±6.800, than in the control group 15.33±0.895, 39.51±3.810, the difference was statistically significant(P<0.05), both were lower than control group 3.61±1.481,29.00±8.179,there was no statistically significant difference(P>0.05);3. immunohistochemical detection of inflammatory factors: the control group of IFN-gamma, the expression of TNF alpha respectively 0.51±0.035, 0.41±0.032, were higher than in control group 16±0.041, 0.14±0.019, the difference was statistically significant(P<0.05), were higher than IDO inhibitor group 0.49±0.028, 0.41±0.02, there was no statistically significant difference(P>0.05).Conclusion:IDO inhibitor have no effect on expression of inflammatory cytokines.However,they can reduce the synthesis of serum KYN and KYNA, and improve the spatial learning and memory ability in rats with cognitive impairment caused by chronic cerebral hypoperfusion.