【作者】 王敏；

【导师】 韩彦青；

【作者基本信息】 山西医科大学 ， 神经病学（专业学位）， 2015， 硕士

【摘要】 目的:观察使用吲哚胺2,3-二加氧酶(Indoleamine 2,3–dioxygenase,IDO)抑制剂后慢性脑低灌注大鼠血犬尿氨酸(KYN)、犬尿喹啉酸(KYNA)水平的变化,海马CA1区干扰素(IFN-γ)、肿瘤坏死因子(TNF-α)的表达,及对慢性脑低灌注导致认知功能损害的行为学改善。方法:1.Morris水迷宫检测双侧结扎经总动脉后的各组大鼠空间学习与记忆能力变化,以及使用IDO抑制剂后大鼠的空间学习记忆能力的改善。2.高效液相色谱-荧光检测法对假手术组、对照组、IDO抑制剂大鼠的血KYN及KYNA的水平的测定。3.各组大鼠海马CA1区干扰素-γ、肿瘤坏死因子-α的表达,采取免疫组化的方法。结果:1.水迷宫行为学检测结果:第4、5天IDO抑制剂组大鼠逃避潜伏期分别为(23.41±29.75)、(21.45±29.91),均短于对照组的(49.37±10.47)、(37.22±28.39),差异有统计学意义(P<0.05),均高于假手术组的(17.12±12.2)、(10.90±10.14),差异无统计学意义(P>0.05);IDO抑制剂组平台象限游泳距离百分比为(0.54±0.044),高于对照组的(0.29±0.063),差异有统计学意义(P<0.05);低于假手术组的(0.56±0.028),差异无统计学意义(P>0.05);2.高效液相色谱-荧光检测法检测结果:IDO抑制剂组血KYN及KYNA水平分别为(1.69±0.936)、(25.66±6.800),均低于对照组的(15.33±0.895)、(39.51±3.810),差异有统计学意义(P<0.05),均低于假手术组的(3.61±1.481)、(29.00±8.179)差异无统计学意义(P>0.05);3.免疫组化检测结果:对照组IFN-γ、TNF-α的表达分别为(0.51±0.035)、(0.41±0.032),均高于假手术组的(16±0.041)、(0.14±0.019),差异有统计学意义(P<0.05),均高于IDO抑制剂组的(0.49±0.028)、(0.41±0.02),差异无统计学意义(P>0.05)。结论:IDO抑制剂不影响炎性因子的表达,但可以减少血清中KYN及KYNA的合成,可以改善慢性脑低灌注致认知障碍大鼠的空间学习及记忆能力。更多还原

【Abstract】 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.更多还原