培元解郁方对急性应激BALB/c小鼠的抗抑郁作用及TRP-KYN代谢途径的调节

摘要

目的:研究培元解郁方的抗抑郁作用及其对色氨酸(Tryptophan,TRP)-犬尿氨酸(Kynurenine,KYN)途径的调节.方法:急性应激造成小鼠抑郁模型,采用Noldus EthoVision XT9系统采集分析小鼠强迫游泳不动时间,采用HPLC-MS/MS技术检测脑组织色氨酸、犬尿氨酸含量,实时荧光定量PCR检测肝组织中色氨酸2,3-双加氧酶(Tryptophan 2,3-dioxygenaes,TDO)的mRNA表达水平.结果:急性应激可以引起小鼠不动时间延长,肝组织TDO活性增高,TDO mRNA表达增多.天丝饮、培元解郁方能缩短小鼠不动时间(P<0.05),降低TDOmRNA表达数量,天丝饮尚有明显的抑制喹啉酸(Quinolinic acid,Q)作用.结论:天丝饮、培元解郁方具有抗抑郁药物样作用,这一作用可能与减少急性应激后血清皮质酮(Corticosterone,C)的含量,降低TDOmRNA的表达有关;天丝饮表现出明显的抑制神经毒性的作用可能与调节KYN代谢产物有关.%Objective:To study the antidepressant effects of Peiyuan Jieyu Decoction and its regulation on the tryptophan-kynurenine (TRP-KYN)pathway.Methods:The mice model was established by acute stress.The immobility time in forced swimming test was acquired and analysed by Noldus EthoVision XT9 system.The content of tryptophan and kynurenine in brain tissue were detected by HPLC-MS/MS technique.The mRNA expression level of tryptophan 2,3-dioxygenaes (TDO) in liver tissue was detected by real-time PCR.Results:Acute stess induced prolong of immobility time of Balb/c mice (P<0.05).The TDO activity in liver tissue and the TDO mRNA expression level increased (P<0.01).Tiansi Decoction and Peiyuan Jieyu Decoction could shorten the immobility time of mice (P<0.05) and reduce the TDO mRNA expression.The inhibitory effect of Quinolinic acid by Tiansi Decoction was more significant.Conclusion:Tiansi Decoction and Peiyuan Jieyu Decoction has antidepressant effect.This effect may be related to the decrease of serum corticosterone levels after acute stress and the reduction of the TDO mRNA expression.Tiansi Decoction shows obvious inhibition to neurotoxins which may be related to the regulation of KYN metabolites.