Yang Zhihui, Zhao Andong, Li Zhongdong, Ge Hua, Li Tonghua, Zhang Fucheng, Zhan Hao, Wang Jianchang
Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032 Shanxi, China; Department of Pharmacology, General Hospital of Air Force, PLA, Beijing 100142, China.
Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032 Shanxi, China; Institute of Aviation Medicine, Air Force, Beijing 100142, China.
J Pharm Biomed Anal. 2016 Jun 5;125:77-84. doi: 10.1016/j.jpba.2016.03.016. Epub 2016 Mar 8.
Positive acceleration (+Gz) in the head-to-foot direction generated by modern high-performance fighter jets during flight maneuvers is characterized by high G values and a rapid rate of acceleration, and is often long in duration and a repeated occurrence. The acceleration overload far exceeds the pilot's physiological tolerance limits and causes considerable strain on several organ systems. Despite the importance of monitoring pathophysiological alterations related to +Gz exposure, we lack a complete explanation of the pathophysiology of +Gz exposure. Ginkgo biloba extract (GBE) is a classic traditional Chinese medicine (TCM) that might exert a protective effect against +Gz exposure. However, its mechanism remains unclear. Here, a metabolomics approach based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS) was used to characterize +Gz-induced metabolic fluctuations in a rat model and to evaluate the protective effect of GBE. Using partial least-squares discriminant analysis for the classification and selection of biomarkers, eighteen serum metabolites related to +Gz exposure were identified, and were found to primarily involve the fatty acid β-oxidation pathway, glycerophospholipid metabolism, phospholipid metabolism, bile acid metabolism, purine metabolism and lysine metabolism. Taking these potential biomarkers as screening indexes, we found that GBE could reverse the pathological process of +Gz exposure by partially regulating the perturbed fatty acid β-oxidation pathway, glycerophospholipid metabolism, purine metabolism and lysine metabolism. This indicates that UHPLC-Q-TOFMS-based metabolomics provides a powerful tool to reveal serum metabolic fluctuations in response to +Gz exposure and to study the mechanism underlying TCM.
现代高性能战斗机在飞行机动过程中产生的头至脚方向的正向加速度（+Gz）具有高G值、快速加速度的特点，且持续时间长、反复出现。这种加速度过载远远超过飞行员的生理耐受极限，会对多个器官系统造成相当大的压力。尽管监测与+Gz暴露相关的病理生理改变很重要，但我们对+Gz暴露的病理生理学仍缺乏完整的解释。银杏叶提取物（GBE）是一种经典的中药，可能对+Gz暴露具有保护作用。然而，其作用机制尚不清楚。在此，采用基于超高效液相色谱-四极杆飞行时间质谱联用（UHPLC-Q-TOFMS）的代谢组学方法，对大鼠模型中+Gz诱导的代谢波动进行表征，并评估GBE的保护作用。通过偏最小二乘判别分析对生物标志物进行分类和筛选，鉴定出18种与+Gz暴露相关的血清代谢物，发现它们主要涉及脂肪酸β-氧化途径、甘油磷脂代谢、磷脂代谢、胆汁酸代谢、嘌呤代谢和赖氨酸代谢。以这些潜在的生物标志物为筛选指标，我们发现GBE可以通过部分调节受干扰的脂肪酸β-氧化途径、甘油磷脂代谢、嘌呤代谢和赖氨酸代谢来逆转+Gz暴露的病理过程。这表明基于UHPLC-Q-TOFMS的代谢组学为揭示+Gz暴露后的血清代谢波动以及研究中药作用机制提供了一个强大的工具。
