培元解郁方对IFNγ诱导抑郁模型大鼠的抗抑郁作用及TRY-KYN代谢途径的调节

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目的:研究培元解郁方的抗抑郁作用及其对色氨酸(TRP)-犬尿氨酸(KYN)代谢的影响。方法:使用干扰素γ(IFNγ)腹腔注射(100U/300g)造成大鼠抑郁模型,检测大鼠1%蔗糖水消耗,采用Noldus Etho Vision XT9系统采集分析大鼠敞箱、Morris水迷宫行为,采用HPLC-MS/MS技术检测脑组织TRP、KYN含量,实时荧光定量PCR检测脑组织中吲哚胺2,3-双加痒酶(IDO)mRNA表达。结果:IFNγ注射14d后可以引起模型组大鼠敞箱水平活动、垂直活动减少(P<0.01,P<0.05),蔗糖水消耗与正常组比较显著减少(P<0.01),Morris水迷宫定位航行试验中潜伏期延长(P<0.05),空间搜索试验穿越平台次数减少(P<0.01)。脑组织IDO活性增高,IDO mRNA表达增多(P<0.05)。培元解郁方能增加大鼠水平活动及垂直活动次数,增加大鼠蔗糖消耗率(P<0.05),缩短水迷宫中潜伏期(P<0.01),增加穿越平台的次数(P<0.05),并能抑制IDO活性和IDO mRNA表达(P<0.05)。结论:培元解郁方具有抗抑郁药物样作用,其机制与IDO抑制有关。培元解郁方在改善敞箱行为和学习记忆行为方面优于四逆散和天丝饮,可能与合方后IDO抑制作用增强有关。 Objective: To study the antidepressant effect of Peiyu Jieyu Decoction and its effect on the metabolism of tryptophan (TRP) - kynurenine (KYN). Methods: The rat model of depression was induced by intraperitoneal injection of interferon γ (IFNγ) (100U / 300g), the consumption of 1% sucrose in rats was measured. The behavior of rats in the open and Morris water maze was detected by Noldus Etho Vision XT9 system. The contents of TRP and KYN in brain tissue were detected by HPLC-MS / MS. The mRNA expression of indoleamine 2,3-diacyl-decanoate (IDO) in brain tissue was detected by real-time fluorescence quantitative PCR. RESULTS: After 14 days of IFNγ injection, the rats in the model group were able to open their arms to open their arms and lower their vertical activities (P <0.01, P <0.05). The sucrose water consumption was significantly decreased compared with that of the normal group (P <0.01) The incubation period was prolonged (P <0.05) and the number of space search trials across the platform was decreased (P <0.01). Increased IDO activity and IDO mRNA expression in brain tissue (P <0.05). Peiyuan Jieyu can increase the level of horizontal activity and vertical activity in rats, increase the sucrose consumption rate (P <0.05), shorten the latent period in the water maze (P <0.01), increase the number of crossing the platform (P <0.05) Inhibition of IDO activity and IDO mRNA expression (P <0.05). Conclusion: Peiyuan Jieyu Decoction has antidepressant drug-like effect, and its mechanism is related to IDO inhibition. Peiyuan Jieyu Fang better open-box behavior and learning and memory behavior than Sini San and Tencel, may be associated with the IDO inhibition after the enhancement.
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