Pediatric Intensive Care Unit, Medical School, University of Crete, Heraklion, Crete, Greece.
Postgraduate Program "Emergencies and Intensive Care in Children Adolescents and Young Adults", Medical School, University of Crete, Heraklion, Crete, Greece.
Sci Rep. 2021 Jan 13;11(1):1049. doi: 10.1038/s41598-020-78208-2.
Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.
脓毒症是一种宿主对感染的失调反应，与毁灭性的结局有关。最近，人们的兴趣已经转移到凋亡和抗凋亡的病理生物学上。凋亡是通过 caspase 的激活来执行的，caspase 受许多抗凋亡蛋白的调节，如生存素。生存素和 caspase 对脓毒症的反应尚未阐明。这是一项多中心前瞻性观察研究，涉及脓毒症患者（n=107）、创伤性全身炎症反应综合征（SIRS）患者（n=75）和健康对照者（n=89）。通过实时定量聚合酶链反应，在外周血白细胞中定量检测不同生存素剪接变体（野生型-WT、ΔEx3、2B、3B）的生存素表达。通过酶联免疫吸附试验测量生存素-WT、caspase-3 和 -9 血清蛋白浓度来确定凋亡或抗凋亡倾向。在 SIRS 和脓毒症中，生存素-WT、-2B、-ΔΕx3 mRNA、生存素蛋白和 caspase 呈递增性增加，而 3B 在脓毒症中被抑制（p<0.05）。生存素与 IL-8 和 caspase-9 相关（p<0.01）。为了区分脓毒症，caspase-9 获得了最佳的受试者工作特征曲线（AUROC）为 0.95。在预测死亡率方面，caspase-9 和生存素蛋白的 AUROC 为 0.70。总之，特定的凋亡和抗凋亡途径可能是脓毒症未来研究的有吸引力的目标。
