Reséndiz-Martínez Judith, Asbun-Bojalil Juan, Huerta-Yepez Sara, Vega Mario
Servicio de Terapia Intensiva Pediátrica, Hospital General Dr Gaudencio González Garza, Centro Medico La Raza IMSS, 02990 Mexico City, Mexico.
Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México Federico Gómez S.S.A, 06720 Mexico City, Mexico.
Mol Med Rep. 2017 May;15(5):2433-2442. doi: 10.3892/mmr.2017.6310. Epub 2017 Mar 9.
Multiple organ dysfunction (MOD) is a lethal complication in children with sepsis. Apoptosis of several cell types is involved in this process, and it is associated with increased Fas cell surface death receptor (Fas) expression. As YY1 transcription factor (YY1) negatively regulates the expression of Fas in cancer models, and is associated with the clinical outcome, it may be important in MOD. The present study aimed to determine the association between the expression of Fas, YY1 and apoptosis in children with sepsis, and its association with MOD, these factors were analyzed in 30 pediatric patients that had been diagnosed with sepsis. Peripheral blood mononuclear cells were purified from patients, and YY1 and Fas protein expression was assessed by immunocytochemistry. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick‑end labeling. Sepsis was monitored using clinical parameters, pediatric logistic organ dysfunction (PELOD) score and the pediatric mortality index. The results demonstrated that Fas expression was directly correlated with apoptosis levels and the expression of YY1 was inversely correlated with apoptosis levels. Patients with high levels of apoptosis exhibited increased disease severity and poor clinical outcome. Notably, the findings of the present study demonstrated that there were higher survival rates in patients with high YY1 expression, compared with those with low YY1 expression. Additionally, patients with MOD exhibited lower proportions of apoptotic cells compared with sepsis patients without MOD. Furthermore, the PELOD score was positively correlated with Fas and inversely correlated with YY1 expression. Finally, high apoptosis and low YY1 expression were prognostic factors associated with poor survival rates. These data suggested that YY1 may be important for apoptosis induction via the regulation of Fas during sepsis. Therefore, Fas may be a potential therapeutic target to prevent MOD through regulation of YY1 expression. Furthermore, YY1 and Fas expression in PBMCs may be used to as prognostic markers.
多器官功能障碍（MOD）是脓毒症患儿的一种致命并发症。多种细胞类型的凋亡参与了这一过程，且与Fas细胞表面死亡受体（Fas）表达增加有关。由于YY1转录因子（YY1）在癌症模型中负向调节Fas的表达，并与临床结局相关，其在MOD中可能具有重要作用。本研究旨在确定脓毒症患儿中Fas、YY1的表达与凋亡之间的关联，以及其与MOD的关系，对30例诊断为脓毒症的儿科患者的这些因素进行了分析。从患者中纯化外周血单个核细胞，通过免疫细胞化学评估YY1和Fas蛋白表达。采用末端脱氧核苷酸转移酶dUTP缺口末端标记法测定凋亡情况。使用临床参数、儿科逻辑器官功能障碍（PELOD）评分和儿科死亡率指数监测脓毒症。结果表明，Fas表达与凋亡水平直接相关，而YY1表达与凋亡水平呈负相关。凋亡水平高的患者疾病严重程度增加，临床结局较差。值得注意的是，本研究结果表明，与YY1表达低的患者相比，YY1表达高的患者生存率更高。此外，与无MOD的脓毒症患者相比，MOD患者的凋亡细胞比例更低。此外，PELOD评分与Fas呈正相关，与YY1表达呈负相关。最后，高凋亡和低YY1表达是与低生存率相关的预后因素。这些数据表明，YY1可能通过在脓毒症期间调节Fas对凋亡诱导起重要作用。因此，Fas可能是通过调节YY1表达来预防MOD的潜在治疗靶点。此外，外周血单个核细胞中YY1和Fas的表达可作为预后标志物。
