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目的:研究四逆散对色氨酸(TRP)-犬尿氨酸(KYN)代谢途径及其关键代谢酶吲哚胺2,3过氧化酶(IDO)活性和含量的影响。方法:脂多糖(LPS)1mg/kg腹腔注射造成小鼠抑郁模型,采用ELISA方法检测血清γ干扰素(IFN-γ)含量,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IDO的m RNA表达水平。结果:与正常组比较,LPS注射4h后可以引起模型组小鼠不动时间延长,血清IFN-γ明显增高(P<0.05),同时,脑组织IDO活性、IDO m RNA表达增多(P<0.01)。与模型组比较,四逆散能缩短小鼠不动时间,降低血清IFN-γ含量(P<0.05),且能抑制IDO活性及m RNA表达数量(P<0.01)。结论:四逆散阻断了炎性因子诱导IDO激活途径,抑制了IDO的活性,并降低其含量,通过调节TRP-KYN代谢产生抗抑郁作用。
Objective: To investigate the effects of Sini Decoction on the metabolic pathway of tryptophan (TRP) - kynurenine (KYN) and the activities and contents of indoleamine 2,3 peroxidase (IDO). Methods: The mice model of depression was induced by intraperitoneal injection of lipopolysaccharide (LPS) 1 mg / kg. The levels of IFN-γ in serum were detected by ELISA. The contents of TRP and KYN in brain tissues were detected by HPLC-MS / PCR was used to detect the mRNA expression of IDO in brain tissue. Results: Compared with the normal group, LPS injection for 4 h caused immobility time and serum IFN-γ in the model group increased significantly (P <0.05), while IDO activity and IDO m RNA expression in the brain tissue increased (P <0.01 ). Compared with the model group, Sini Decoction could shorten the immobility time, decrease the level of serum IFN-γ (P <0.05), and inhibit IDO activity and m RNA expression (P <0.01). Conclusion: Sini Decoction blocks the activation of IDO induced by inflammatory cytokines, inhibits the activity of IDO and decreases its content, and produces antidepressant effect by regulating the metabolism of TRP-KYN.