抑郁症发病机理中的重要调节因子:吲哚胺2,3-双加氧酶

An Important Regulation Factor in Depression: Indoleamine 2,3-dioxygenase

抑郁症的发病存在多种假说,其中较为公认的有细胞因子假说,下丘脑-垂体-肾上腺皮质(hypothalamus-pituitary-adrenocortical,HPA)轴假说,单胺能假说,神经可塑性假说等,不同假说可能从不同角度探讨抑郁症的病理机制,但各种假说都与吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)的调节有关。IDO是一种色氨酸降解酶,其活性能够被前炎性细胞因子所增强。IDO活性的增强使色氨酸更多地代谢为犬尿氨酸(kynurenine,KYN),从而可能导致生成5-羟色胺(serotonin,5-HT)的原料不足,5-HT生成减少。而且,色氨酸-犬尿氨酸代谢通路的下游产物犬尿喹啉酸(kynurenicacid,KYNA),喹啉酸(quinolinic acid,QUIN)及3-羟基犬尿氨酸(3-hydroxykynurenine,3HKYN)等影响神经元的再生与退化。另外,应激激素也可以通过色氨酸2,3-双加氧酶(tryptophan 2,3-dioxygenaes,TDO)或免疫系统影响IDO的功能。IDO是抑郁症多种假说病理机制中的共同调节因子,可能在抑郁病的发病中具有重要作用。

There are different theories and hypotheses cytokine hypothesis, hypothalamic-pituitary-adrenal related to the etiology of depression. Among them, axis hypothesis, monoamine hypothesis and neuroplasticity hypothesis are much more widely accepted. These hypotheses may discuss depression from different points, but they are all related to indoleamine 2, 3-dioxygenase （IDO）. IDO is a kind of enzyme which can convert tryptophan （TRP）, the precursor of serotonin to kynurenine （KYN）. It can be activated by some proinflammatory cytokines. Once activated, more TRP would be siphoned from the formation of serotonin to KYN, which may cause a reduction in serotonin production. IDO can also be activated by stress hormones through tryptophan 2, 3-dioxygenase （TDO） or immune system. In addition, some downstream metabolites of KYN, such as kynurenic acid （KYNA）, quinolinic acid （QUIN） and 3-hydroxykynurenine （3HKYN）, may contribute to neuroplasticity, as they are neurotoxic or neuroprotective. IDO, the mutual regulation factor among these theories, may play an important role in the onset of depression.