目的:研究培元解郁方的抗抑郁作用以及对色氨酸(TRY)-犬尿氨酸(KYN)代谢的调节机制.方法:建立氢化可的松大鼠抑郁模型,以蔗糖消耗反映大鼠的抑郁状态,采用高效液相-质谱联用( HPLC-MS/MS)技术检测脑组织KYN、TRY、喹啉酸(QUIN)、犬尿烯酸(KA)含量,实时荧光定量PCR技术测定肝组织中色氨酸2,3-双加氧酶(TDO)mRNA表达水平和脑组织海马中吲哚胺2,3-双加氧酶(IDO)、5-HT1A的mRNA表达.结果:造模21 d后,大鼠对蔗糖的偏好降低,KYN/TRY比值升高,QUIN含量升高,KA含量降低,TDO mRNA的表达水平增加,5-HT1AmRNA的表达水平降低,差异有统计学意义(P<0.05).各给药组能提高大鼠对蔗糖的偏好,差异有统计学意义(P<0.05).各给药组均能显著降低KYN/TRY比值,差异有统计学意义(P<0.05),培元解郁方中剂量组和天丝饮组能显著提高KA的含量,降低QUIN的含量,差异有统计学意义(P<0.05).天丝饮能明显降低肝脏中TDO和海马中IDO mRNA的表达,差异有统计学意义(P<0.05).四逆散和培元解郁方中、高剂量能够增加海马中5-HT1AmRNA的表达,差异有统计学意义(P<0.05).结论:天丝饮、四逆散和培元解郁方均有抗抑郁药样作用,机制与降低TRY-KYN代谢的关键酶mRNA表达,降低神经毒性代谢产物和增加神经保护性代谢产物,从而提高神经元保护作用,以及增加5-HT1A的mRNA表达有关.
Objective:To study the antidepressant effects of Peiyuan Jieyu Decoction and the regulatory mechanism of the trypto -phan-kynurenine (TRY-KYN) metabolic pathway.Methods:The rat model of depression induced by intraperitoneal injection hy-drocortisone was built.The symptoms of depression were observed by sucrose preference experiment .The contents of tryptophane , kynurenine,kynurenic acid and quinaldinic acid in brain tissue were detected by HPLC -MS/MS technique.The mRNA expression levels of TDO in liver tissue ,IDO and 5-HT1Ain brain tissue were detected by using real-time PCR.Results:After 21 days′acute stress,the preference in sucrose was reduced.The ratio of KYN/TRY and the content of QUIN were increased.The content of KA was decreased.The expression of TDO mRNA increased and the expression of 5-HT1AmRNA decreased (P<0.05).The Fluoxe-tine group,Tiansi decoction group ,Sini decoction group ,high dose and middle dose of Peiyuan Jieyu decoction group could improve the preference in sucrose preference experiment (P<0.05).Each treatment group could obviously reduce the ratio of KYN /TRY (P<0.05).Tiansi decoction and middle dose of Peiyuan Jieyu decoction could significantly improve the content of KA ,and de-crease the content of QUIN P<0.05).Tiansi decoction could obviously decrease the expression of TDO mRNA in liver and the ex -pression of IDO mRNA in hippocampus (P<0.05).Sini decoction,middle dose and high dose of Peiyuan Jieyu decoction could increase the expression of 5-HT1AmRNA in hippocampus (P<0.05).Conclusion:Traditional Chinese medicine groups have anti-depressant effects.Its mechanism may be connected with reducing the expression of the key enzyme mRNA in TRY -KYN metabolic pathway,improving the neuron protective effect by reducing neurotoxic metabolites and increasing neuroprotective metabolites ,and increasing the expression of 5-HT1A.