Kazda H, Taylor N, Healy D, Walker D
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Pediatr Res. 1998 Sep;44(3):368-73. doi: 10.1203/00006450-199809000-00017.
A major route of tryptophan metabolism is via the hepatic and cerebral synthesis of kynurenine, a substance subsequently used by astrocytes in the brain for the production of the neuroactive substances kynurenic acid and quinolinic acid. Both kynurenic and quinolinic acids have been implicated in modulating the activity of excitatory amino acid pathways in the brain, the former as a neuroprotectant because of its antagonist properties, and the latter as an excitotoxin because of its agonist actions, at NMDA receptors. We therefore determined the concentrations of tryptophan and kynurenine in maternal venous and umbilical cord blood, and in amniotic fluid, of infants after labor and vaginal delivery, and after delivery by cesarean section. Concentrations of tryptophan and kynurenine were significantly higher in umbilical vein plasma compared with maternal venous plasma. Tryptophan and kynurenine concentrations in umbilical vein plasma and amniotic fluid were significantly higher after labor, compared with samples obtained from infants of the same gestational age delivered by cesarean section. There was no umbilical vein-to-artery concentration difference for kynurenine in samples obtained after either labor or cesarean section, but there was a significant gradient for tryptophan in samples obtained after vaginal delivery, indicating increased transfer of this amino acid during labor. There was a significant correlation between umbilical vein tryptophan and kynurenine concentrations for both the labor and cesarean section groups, and plasma kynurenine concentrations were also significantly correlated with both umbilical vein cortisol concentrations and the duration of the second stage of labor in the vaginally delivered infants. These results suggest that the placental transfer of tryptophan and the fetal synthesis of kynurenine are increased during labor. These findings have implications for understanding the vulnerability of the infant brain to ischemic/hypoxic damage in the perinatal period. By analogy with the adult brain, the molar ratio of these substances is likely to determine the susceptibility of the brain to seizure and excitotoxic damage.
色氨酸代谢的一条主要途径是通过肝脏和大脑合成犬尿氨酸，大脑中的星形胶质细胞随后利用这种物质生成神经活性物质犬尿喹啉酸和喹啉酸。犬尿喹啉酸和喹啉酸都与调节大脑中兴奋性氨基酸途径的活性有关，前者因其拮抗特性而作为神经保护剂，后者因其在N-甲基-D-天冬氨酸（NMDA）受体上的激动剂作用而作为兴奋性毒素。因此，我们测定了经阴道分娩和剖宫产分娩后婴儿的母亲静脉血、脐带血以及羊水中色氨酸和犬尿氨酸的浓度。与母亲静脉血浆相比，脐静脉血浆中色氨酸和犬尿氨酸的浓度显著更高。与剖宫产分娩的同孕周婴儿的样本相比，经阴道分娩后脐静脉血浆和羊水中色氨酸和犬尿氨酸的浓度显著更高。经阴道分娩或剖宫产分娩后采集的样本中，犬尿氨酸的脐静脉与脐动脉浓度无差异，但经阴道分娩后采集的样本中色氨酸存在显著梯度，表明分娩过程中这种氨基酸的转运增加。经阴道分娩组和剖宫产组的脐静脉色氨酸和犬尿氨酸浓度之间存在显著相关性，并且血浆犬尿氨酸浓度也与脐静脉皮质醇浓度以及经阴道分娩婴儿第二产程的持续时间显著相关。这些结果表明，分娩过程中色氨酸的胎盘转运和胎儿犬尿氨酸的合成增加。这些发现对于理解围产期婴儿大脑对缺血/缺氧损伤的易感性具有重要意义。与成人大脑类似，这些物质的摩尔比可能决定大脑对癫痫发作和兴奋性毒性损伤的易感性。
