Effect Of IDO Inhibitor On Hippocampal CA1 Region Cells Apoptosis In Rats With Chronic Cerebral Hypoperfusion

Objective:Observe the change of cell apoptosis in hippocampal CA1 and apoptosis related protein Bcl-2, Bax expression after using rate-limiting enzyme of KP--IDO inhibitor 1-MT at chronic cerebral hypoperfusion model 2VO rats,and the improvement of cognitive impairment.Method:Rats were randomly divided into three groups.Model group and 1-MT group rats were submitted to the modified 2VO method,sham group processing steps as above without common carotid artery ligation.1-MT group were given gavage using 1-MT suspension for14 days,other group using normal saline.Cognitive performances of the animals were tested by Morris water maze test.Apoptosis was assessed by TUNEL staining.Bax and Bcl-2 expression was detected by immunohistochemistry.Results :(1)water maze test:escape latency of 1-MT group in day 4 and 5 were(17.93 ± 3.24),(13,11 ± 1.85),lower than the model group(42.31 ± 6.03),(41.12 ± 4.56)(P <0.05),higher than the shame group(13.86 ± 2.84),(10.59 ± 2.09),the difference was not statistically significant(P> 0.05);1-MT group times of crossing the platform location(4.70 ± 0.60),more than the model group(2.50 ± 0.45)(P <0.05), less than the sham group(4.90 ±0.66)(P<0.05); 1-MT group target quadrant time(26.87 ± 1.82), higher than the model group(21.56 ± 1.74)(P <0.05), lower than the sham group(28.01 ± 1.44)(P> 0.05).(2) The expression of Bax protein were sham-operated group(6.25 ± 1.04), model group(56.43 ± 2.62), 1-MT group(30.16 ± 2.17),pairwise comparison showed that the differences between the groups were statistically significant(P <0.05);Expression of Bcl-2protein were sham-operated group(9.97 ± 2.66), model group(48.67 ± 5.99), 1-MT group(32.67 ± 4.71),compared with the sham group, model group and 1-MT group was significantly increased(P <0.05); Apoptotic cells in rats were sham-operated group(1.79 ±0.41), model group(14.13 ± 1.44), 1-MT group(7.80 ± 1.38),pairwise comparisons showed that the differences between the groups were statistically significant(P <0.05).Conclusion:(1)Apoptosis and Bcl-2,Bax protein expression increased in 2VO rats hippocampal CA1 region,apoptosis involved in pathophysiological changes and cognitive impairment induced by chronic cerebral hypoperfusion in rats;(2)1-MT can inhibit the cognitive impairment,apoptosis and expression of apoptosis related protein in hippocampal CA1 region neurons,but the changes seems insufficient to explain recognize improvement,suggesting that 1-MT probably improve the cognitive through collective effect of apoptosis,inflammation and other mechanisms.