Respirotory Department, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 W. Yanta Road, Xi'an 710061, China.
Cardiovascular Department, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 W. Yanta Road, Xi'an 710061, China.
Nutrients. 2021 Nov 17;13(11):4116. doi: 10.3390/nu13114116.
Recent metabolomics studies have found circulatory metabolism alterations in patients with asthma, indicating that altered metabolites played a significant role in asthma. However, the regulatory mechanisms in asthma, especially in young chronic persistent asthma remain underexplored.
In this study, a prospective cohort of 162 patients diagnosed of asthma admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to December 2019 was used to perform a nested case-control study. Among them, we included 30 patients with chronic persistent asthma between 20 to 35 years old; 30 health control with evenly distributed age and sex were then recruited. Nontargeted metabolomics was applied to identify serum metabolic profiles and altered metabolic pathways.
In vitro, human bronchial epithelial cells (HBECs) line BEAS-2B with the addition of L-citrulline and/or asymmetric dimethylarginine (ADMA) model was utilized and the concentrations of nitric oxide (NO) metabolites were tested to evaluate the therapeutic potential of L-citrulline. The young patients with chronic persistent asthma displayed dysregulated serum metabolic profiles, especially enriched in arginine metabolism. The ratio of L-citrulline to ornithine is associated with blood eosinophil count. In vitro, adding L-citrulline could reverse ADMA-mediated reduction of NOx at lower L-arginine concentration (25 μM), but was ineffective in the higher L-arginine concentration (100 μM) media.
The arginine metabolism balance is of vital importance during the pathogenesis and progression of chronic asthma. L-citrulline could be a powerful approach to restore airway NO production, potentially exhibiting therapeutic benefits among young patients with chronic asthma.
最近的代谢组学研究发现哮喘患者循环代谢发生改变，表明代谢物改变在哮喘中起重要作用。然而，哮喘的调控机制，尤其是在年轻的慢性持续性哮喘中仍未得到充分探索。
本研究采用前瞻性队列研究，纳入 2018 年 1 月至 2019 年 12 月西安交通大学第一附属医院收治的 162 例哮喘患者，进行巢式病例对照研究。其中纳入 30 例年龄在 20-35 岁之间的慢性持续性哮喘患者，然后招募 30 名年龄和性别分布均匀的健康对照者。应用非靶向代谢组学技术鉴定血清代谢谱和改变的代谢途径。
在体外，我们利用人支气管上皮细胞（HBECs）系 BEAS-2B 加入 L-瓜氨酸和/或不对称二甲基精氨酸（ADMA）模型，检测一氧化氮（NO）代谢物的浓度，评估 L-瓜氨酸的治疗潜力。年轻的慢性持续性哮喘患者表现出失调的血清代谢谱，特别是精氨酸代谢富集。L-瓜氨酸与鸟氨酸的比值与血嗜酸性粒细胞计数有关。在体外，添加 L-瓜氨酸可以逆转 ADMA 介导的在较低 L-精氨酸浓度（25 μM）下的 NOx 减少，但在较高 L-精氨酸浓度（100 μM）的培养基中无效。
精氨酸代谢平衡在慢性哮喘的发病机制和进展中至关重要。L-瓜氨酸可能是一种恢复气道 NO 产生的有力方法，可能对年轻的慢性哮喘患者具有治疗益处。
