Lull Melinda E, Carkaci-Salli Nurgul, Freeman Willard M, Myers John L, Midgley Frank M, Thomas Neal J, Kimatian Stephen J, Vrana Kent E, Undar Akif
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Pediatr Res. 2008 Jun;63(6):638-44. doi: 10.1203/PDR.0b013e31816e391f.
It is critical to identify at-risk patients and minimize the deleterious effects of cardiopulmonary bypass (CPB) procedures in pediatric populations. The present study screened the plasma proteome of pediatric patients undergoing CPB procedures to identify potential clinical biomarkers related to tissue damage, inflammation, or other pathologies. Blood samples were collected at five different time points from 10 children undergoing a CPB procedure. Plasma was isolated and analyzed using two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption ionization time of flight mass spectrometry. Levels of differentially regulated proteins identified by two-dimensional differential in-gel electrophoresis, and related proteins were then measured in all time points and patients. As well, associated small molecules and ions were measured. The present study identified 13 proteins and protein isoforms altered in expression, including hemopexin, ceruloplasmin, inter-alpha inhibitor H4, and alpha-2-macroglobulin. Immunoblot analysis revealed significant decreases in each of these proteins during the CPB procedure. Significant changes in the levels of copper, iron, Hb, epinephrine, norepinephrine, and serotonin were observed. The potential markers of pathology (inflammation, oxidative stress) identified during this preliminary study may illuminate opportunities for preventative measures and/or treatments during and following CPB procedures in pediatric patients.
识别高危患者并将小儿群体体外循环（CPB）手术的有害影响降至最低至关重要。本研究对接受CPB手术的小儿患者的血浆蛋白质组进行了筛查，以确定与组织损伤、炎症或其他病理相关的潜在临床生物标志物。从10名接受CPB手术的儿童在五个不同时间点采集血样。分离血浆并使用二维差异凝胶电泳和基质辅助激光解吸电离飞行时间质谱进行分析。然后在所有时间点和患者中测量通过二维差异凝胶电泳鉴定的差异调节蛋白水平以及相关蛋白。此外，还测量了相关的小分子和离子。本研究确定了13种表达改变的蛋白质和蛋白质异构体，包括血红素结合蛋白、铜蓝蛋白、α-抑制因子H4和α-2-巨球蛋白。免疫印迹分析显示在CPB手术期间这些蛋白质中的每一种都有显著下降。观察到铜、铁、血红蛋白、肾上腺素、去甲肾上腺素和血清素水平的显著变化。在这项初步研究中确定的病理（炎症、氧化应激）潜在标志物可能为小儿患者CPB手术期间及之后的预防措施和/或治疗提供机会。
