犬尿氨酸途径在不可逆性牙髓炎中的作用。
The Role of the Kynurenine Pathway in Irreversible Pulpitis.
摘要(中文译文)
目前的治疗方法在局部针对急性疼痛方面的效果有限。这在一定程度上是由于对牙髓炎中活跃的神经炎症途径缺乏了解。在几种情况下，吲哚胺2,3-双加氧酶（IDO）活性的增加与超敏反应和疼痛有关。IDO是犬尿氨酸途径的限速酶，但IDO在牙髓炎中的活性和表达变化尚未得到研究。收集诊断为症状性不可逆牙髓炎（SIP）的牙齿样本，并使用高效液相色谱（HPLC）、定量聚合酶链式反应（PCR）和免疫细胞化学（ICC）检测IDO和犬尿氨酸（KYN）途径其他标志物的水平和活性。随后，来源于牙髓干细胞的成牙本质细胞样细胞（OLCs）在体外用细菌脂多糖和DNA胞嘧啶磷酸鸟嘌呤（CpG）寡核苷酸2006的合成替代物刺激（ODN 2006）。然后使用定量PCR和HPLC质谱分析这些化合物对KYN途径标志物水平和转录的影响。与健康对照组相比，SIP组的IDO活性显著升高。ICC荧光成像显示IDO和KYN与巨噬细胞和神经元纤维的标志物共定位。SIP的定量PCR数据表明，IDO的增加可能会引导KYN途径产生神经炎症分解代谢产物喹啉酸，这是一种与神经保护性犬尿酸的产生相反的代谢产物。在体外给药OLCs和ODN 2006诱导的变化与细菌感染诱导的SIP相似。据我们所知，这篇文章首次证明了IDO活性、神经炎症和SIP中的痛觉通路之间的联系，并将这一过程定位到神经元纤维。这些观察结果突出了犬尿氨酸途径在SIP中的潜在作用，但需要进一步的研究来确定这些变化是否反映在体内神经兴奋性代谢物的水平上。
Abstract
Current therapeutic practices have limited effectiveness at targeting acute pain locally. This is in part due to the lack of understanding of the neuroinflammatory pathways active within pulpitis. Increased activity of inadoleamine 2,3 dioxygenase (IDO) was linked to hypersensitivity and pain in several settings. IDO is the rate-limiting enzyme of the kynurenine pathway, but changes in IDO's activity and expression in pulpitis have not been investigated. Tooth samples with a diagnosis of symptomatic irreversible pulpitis (SIP) were collected, and levels and activity of IDO and other markers of the kynurenine (KYN) pathway were examined using high-performance liquid chromatography (HPLC), quantitative polymerase chain reaction (PCR), and immunocytochemistry (ICC). Subsequently, odontoblast-like cells (OLCs) derived from dental pulp stem cells were stimulated in vitro with bacterial lipopolysaccharide and a synthetic proxy for DNA cytosine-phosphate-guanine (CpG) oligonucleotide 2006 (ODN 2006). The effects of these compounds on KYN pathway marker levels and transcription were then analyzed using quantitative PCR and HPLC mass spectrometry. IDO activity was significantly raised in SIP compared with healthy controls. ICC fluorescent imaging showed that IDO and KYN were colocalized with the markers of macrophages and neuronal fibers. Quantitative PCR data of SIP indicated that increased IDO may direct the KYN pathway toward the generation of the neuroinflammatory catabolite quinolinic acid, a metabolite that is opposite to the production of neuroprotective kynurenic acid. Administration of OLCs with ODN 2006 in vitro induced changes similar to those developed in SIP induced by bacterial infection. To our knowledge, this article is the first to demonstrate links between IDO activity, neuroinflammation, and algogenic pathways in SIP and localize this process to neuronal fibers. These observations highlight the potential role of the kynurenine pathway in SIP, but further investigation is required to determine if these changes are mirrored in the levels of neuroexcitatory metabolites in vivo.
如何引用
AMA
J Coulter, C J Nile, H Lemos, P LoCoco, J Whitworth, R A Valentine, et al. The Role of the Kynurenine Pathway in Irreversible Pulpitis.. Journal of dental research. 2026; doi:10.1177/00220345261416437.
APA
J Coulter, C J Nile, H Lemos, P LoCoco, J Whitworth, R A Valentine, et al (2026). The Role of the Kynurenine Pathway in Irreversible Pulpitis.. Journal of dental research. https://doi.org/10.1177/00220345261416437
GB/T 7714
J Coulter, C J Nile, H Lemos, P LoCoco, J Whitworth, R A Valentine, et al. The Role of the Kynurenine Pathway in Irreversible Pulpitis.[J]. Journal of dental research, 2026 doi:10.1177/00220345261416437.
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