Giambelluca Sonia, Ricci Francesca, Simonato Manuela, Correani Alessio, Casiraghi Costanza, Storti Matteo, Cogo Paola, Salomone Fabrizio, Carnielli Virgilio Paolo
Department of Women's and Children's Health, Padova University Hospital, Padova, Italy.
R&D Department, Chiesi Farmaceutici, Parma, Italy.
J Mass Spectrom. 2018 Jul;53(7):560-564. doi: 10.1002/jms.4088.
Variation of the isotopic abundance of selected nutrients and molecules has been used for pharmacological and kinetics studies under the premise that the administered molecule has a different isotopic enrichment from the isotopic background of the recipient subject. The aim of this study is to test the feasibility of assessing the contribution of exogenous surfactant phospholipids to the endogenous alveolar pool in vivo after exogenous surfactant replacement therapy in rabbits. The study consisted in measuring the consistency of C/ C ratio of disaturated-phosphatidylcholine palmitate (DSPC-PA) in 7 lots of poractant alfa, produced over a year, and among bronchoalveolar lavages of 20 rabbits fed with a standard chow. A pilot study was performed in a rabbit model of lavage-induced surfactant deficiency: 7 control rabbits and 4 treated with exogenous surfactant. The contribution of exogenous surfactant to the alveolar pool was assessed after intra-tracheal administration of 200 mg/kg of poractant alfa. The C content of DSPC-PA was measured by isotope ratio mass spectrometry. The mean DSPC-PA C/ C ratio of the 7 lots of poractant alfa was -18.8‰ with a SD of 0.1‰ (range: -18.9‰; -18.6‰). The mean C/ C ratio of surfactant DSPC recovered from the lung lavage of 20 rabbits was -28.8 ± 1.2‰ (range: -31.7‰; -25.7‰). The contribution of exogenous surfactant to the total alveolar surfactant could be calculated in the treated rabbits, and it ranged from 83.9% to 89.6%. This pilot study describes a novel method to measure the contribution of the exogenous surfactant to the alveolar pool. This method is based on the natural variation of C, and therefore it does not require the use of chemically synthetized tracers. This method could be useful in human research and especially in surfactant replacement studies in preterm infants.
在给药分子的同位素富集与受体对象的同位素背景不同的前提下，选定营养素和分子的同位素丰度变化已用于药理学和动力学研究。本研究的目的是测试评估外源性表面活性剂磷脂在兔外源性表面活性剂替代治疗后对体内内源性肺泡池贡献的可行性。该研究包括测量一年中生产的7批猪肺磷脂中饱和磷脂酰胆碱棕榈酸酯（DSPC-PA）的(^{13}C/^{12}C)比值的一致性，以及20只喂食标准饲料的兔子支气管肺泡灌洗物中的该比值。在灌洗诱导的表面活性剂缺乏的兔模型中进行了一项初步研究：7只对照兔和4只接受外源性表面活性剂治疗的兔。在气管内给予200mg/kg猪肺磷脂后，评估外源性表面活性剂对肺泡池的贡献。通过同位素比率质谱法测量DSPC-PA的(^{13}C)含量。7批猪肺磷脂的平均DSPC-PA(^{13}C/^{12}C)比值为-18.8‰，标准差为0.1‰（范围：-18.9‰；-18.6‰）。从20只兔子的肺灌洗物中回收的表面活性剂DSPC的平均(^{13}C/^{12}C)比值为-28.8±1.2‰（范围：-31.7‰；-25.7‰）。可以计算出外源性表面活性剂对治疗兔总肺泡表面活性剂的贡献，其范围为83.9%至89.6%。这项初步研究描述了一种测量外源性表面活性剂对肺泡池贡献的新方法。该方法基于(^{13}C)的自然变化，因此不需要使用化学合成示踪剂。该方法可能对人体研究有用，特别是对早产儿的表面活性剂替代研究。
