犬尿素通路在氯胺酮抗抑郁中的作用

Role of kynurenine pathway in the antidepressant effects of ketamine

目的 观察氯胺酮抗抑郁症过程中大鼠海马IL-1β、吲哚胺2,3-二加氧酶（IDO）、色氨酸（TRP）、犬尿素（KYN）的变化,探讨犬尿素通路在氯胺酮抗抑郁机制中的作用.方法 雄性Wistar大鼠18只,200～250 g,随机均分为三组：抑郁组（D组）、氯胺酮组（K组）和对照组（C组）.D组和K组经过21 d慢性不可预知应激试验,建立大鼠慢性抑郁模型.第22天分别腹腔注射相同容积生理盐水（C组和D组）或氯胺酮10 mg/kg（K组）,给药后30 min强迫游泳6 min,记录后5 min不动时间.行为学测试后,取大鼠海马组织,采用ELISA法测定IL-lβ、IDO、TRP及KYN的含量.结果 与C组比较,D组和K组强迫游泳不动时间明显增多（P＜0.05或P＜0.01）,D组IL-1β、IDO含量及KYN/TRP比值明显升高（P＜0.05）.与D组比较,K组强迫游泳不动时间明显减少（P＜0.0l）,IL-1β、IDO含量及KYN/TRP比值明显降低（P＜0.05）;C组与K组差异无统计学意义.结论 氯胺酮可通过下调KYN通路发挥抗抑郁作用.

Objective To observe the changes of hippocampal levels of IL-1β,IDO,tryptophan （TRP）,kynurenine （KYN） during ketamine＇s antidepressant effects in rats,and explore the role of kynurenine pathway.Methods A total of 18 male Wistar rats （200-250 g） were randomly divided into 3 groups （n =6）：control group （group C）,depressed group （group D）,and ketamine group （group K）.Rats in groups D and K were insulted in the chronic unpredictable stress test for 21 d.On day 22,rats were injected with the same volume of saline （group C and group D） or ketamine 10 mg/kg （group K）.The forced swimming test （FST） of 6 min was conducted and the immobility time of last 5 min was also recorded.Rats were then decapitated and the hippocampus was harvested to determine the levels of IL-1β,IDO,TRP,and KYN using an enzyme-linked immunosorbent assay.Results Compared with group C,the immobility time was increased in group D and group K （P〈 0.05 or P〈0.01）.The contents of IL-1β,IDO,and TRP/KYN ratio were up-regulated in group D （P〈0.05）.Compared with group D,the immobility time was decreased （P〈0.01） and the contents of IL-1β,IDO,and TRP/KYN ratio were down-regulated significantly in group K （P〈0.05）.There was no significant difference between group C and group K.Conclusion The antidepressant effect of ketamine on rat is acting through down-regulating kynurenine pathway.