The liver is the pivotal metabolic organ primarily responsible for metabolic activities, detoxification and regulation of carbohydrate, protein, amino acid, and lipid metabolism. However, very little is known about the complicated pathophysiologic mechanisms of liver injury result from ionizing radiation exposure. Therefore, a pseudotargeted metabolomics approach based on gas chromatography–tandem mass spectrometry with selected reaction monitoring (GC–MS-SRM) was developed to study metabolic alterations of liver tissues in radiation-induced hepatic injury. The pseudotargeted GC–MS-SRM method was validated with satisfactory analytical characteristics in terms of precision, linearity, sensitivity and recovery. Compared to the SIM-based approach, the SRM scanning method had mildly better precision, higher sensitivity, and wider linear ranges. A total of 37 differential metabolites associated with radiation-induced hepatic injury were identified using the GC–MS-SRM metabolomics method. Global metabolic clustering analysis showed that amino acids, carbohydrates, unsaturated fatty acids, organic acids, metabolites associated with pyrimidine metabolism, ubiquinone biosynthesis and oxidative phosphorylation appeared significantly declined after high dose irradiation exposure, whereas metabolites related to lysine catabolism, glycerolipid metabolism and glutathione metabolism presented the opposite behavior. These changes indicate energy deficiency, antioxidant defense damage, accumulation of ammonia and lipid oxidation of liver tissues in response to radiation exposure. It is shown that the developed pseudotargeted method based on GC–MS-SRM is a useful tool for metabolomics study.

肝脏是关键的代谢器官，主要负责代谢活动，排毒和调节碳水化合物，蛋白质，氨基酸和脂质代谢。但是，对于电离辐射暴露导致的肝损伤的复杂病理生理机制知之甚少。因此，开发了一种基于气相色谱-串联质谱联用选择性反应监测（GC-MS-SRM）的伪靶向代谢组学方法，以研究放射性肝损伤中肝组织的代谢变化。伪靶向GC-MS-SRM方法在精密度，线性，灵敏度和回收率方面均具有令人满意的分析特性，从而得到验证。与基于SIM的方法相比，SRM扫描方法具有适度更好的精度，更高的灵敏度和更宽的线性范围。使用GC-MS-SRM代谢组学方法，共鉴定出37种与放射性肝损伤相关的代谢物。全球代谢聚类分析表明，高剂量辐照后氨基酸，碳水化合物，不饱和脂肪酸，有机酸，与嘧啶代谢，泛醌生物合成和氧化磷酸化有关的代谢产物明显减少，而与赖氨酸分解代谢，甘油脂代谢和谷胱甘肽代谢有关的代谢产物呈现相反的行为。这些变化表明能量不足，抗氧化剂防御损伤，氨积累和肝脏组织响应辐射暴露而发生脂质氧化。结果表明，基于GC-MS-SRM的伪靶向方法是进行代谢组学研究的有用工具。