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

目的:研究四逆散、天丝饮、培元解郁方的抗抑郁作用及其对血清皮质酮含量和色氨酸(TRP)-犬尿氨酸(KYN)途径关键代谢酶色氨酸2,3-双加氧酶(TDO)的影响。方法:使用束缚加噪声造成小鼠抑郁模型,采用Noldus Etho Vision XT9系统采集分析小鼠强迫游泳不动时间,采用HPLC-MS/MS技术检测血清色氨酸(TRP)、犬尿氨酸(KYN)、犬尿烯酸(KA)、喹啉酸(Q)、皮质酮(C)含量,实时荧光定量PCR检测肝组织中TDO的mRNA表达水平。结果:束缚加噪声应激5d后可以引起模型组小鼠强迫游泳不动时间延长,血清皮质酮含量增高,KYN/TRP、KYN/KA比值升高,KYN/Q比值降低。四逆散、天丝饮、培元解郁方能缩短小鼠不动时间(P0.01),降低血清皮质酮含量(P0.05),提高KYN/TRP、KYN/Q比值(P0.05),降低KYN/KA比值。结论:四逆散、天丝饮、培元解郁方具有抗抑郁药物样作用,这一作用与对抗应激引发的血清皮质酮升高,抑制色氨酸-犬尿氨酸代谢途径中的神经毒性代谢产物产生并提高神经保护作用有关。

Antidepressant Effects of Peiyuan Jieyu Decoction on Chronic Stress BALB/C Mice and Its Regulatory Mechanism on TRY-KYN Metabolism

To study the influence of antidepressant effects of Sini Powder, Tiansi Liquid, and Peiyuan Jieyu Decoction on corticosrone and tryptophan 2, 3-double enzyme (TDO) and key metabolism enzyme of the tryptophan-kynurenine (TRP-KYN) pathway. Methods:The mice model was established by chronic stress. The immobility time in forced swimming test was acquired and analysed by Noldus EthoVision XT9 system. Tryptophane, kynurenine, kynurenic acid, quinaldinic acid and corticosrone in serum were detected by HPLC-MS/MS technique. The mRNA expression level of TDO in liver was detected by real-time PCR. Results:After five days chronic stress, the immobility time of model group mice was prolonged. The serum corticosterone levels, KYN/TRP and KYN/KA specific value increased and KYN/Q specific value decreased. Tiansi Liquid, Sini Powder and Peiyuan Jieyu Decoction could shorten the immobility time of mice (P<0.1). It could also cut the corticosterone levels (P<0.05); increased KYN/TRP and KYN/Q specific value (P<0.05) and reduced the KYN/KA specific value. Conclusion:Sini Powder, Tiansi Liquid and Peiyuan Jieyu Decoction have antidepressant effect. The mechanism may be related to the increase of serum corticosterone induced by stress reaction and the reduce of neurotoxicity during the TRY-KYN metabolim and improvement of nerve protection.