Huang Wei, Wang Xiaoting, Zhang Hongmin, Wang Guangjian, Liu Dawei
Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Med (Lausanne). 2021 May 13;8:642749. doi: 10.3389/fmed.2021.642749. eCollection 2021.
Fission1 (Fis1) and parkin are key proteins related to mitochondrial fission and mitophagy, respectively. This study aimed to assess the prognostic value of the Fis1/parkin ratio as a biomarker in patients with sepsis. Consecutive patients with sepsis ( = 133) or simple infection ( = 24) were enrolled within 24 h of arrival at the intensive care unit (ICU). Serum levels of Fis1, parkin, mitofusin2 (Mfn2), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) were measured by enzyme-linked immunosorbent assay (ELISA) upon ICU admission. Clinical parameters and standard laboratory test data were also collected. All patients received follow-up for at least 28 days. Patients with sepsis presented with significantly decreased serum levels of parkin, Mfn2, and PGC-1α, but an increased serum Fis1 level and Fis1/parkin, Fis1/Mfn2, and Fis1/PGC-1α ratios at ICU admission. Relative to patients with simple infections, the ratios were remarkably elevated in septic patients-particularly septic shock patients. The area under the receiver operating characteristic (ROC) curve of the Fis1/parkin ratio was greater than that of Fis1, parkin, Mfn2, and PGC-1α levels as well as that of the Fis1/Mfn2 and Fis1/PGC-1α ratios for prediction of 28-day mortality due to sepsis. All of the ratios were significantly higher in non-survivors than survivors at the 28-day follow-up examination. Fis1/parkin ratio was found to be an independent predictor of 28-day mortality in patients with sepsis. The Fis1/parkin ratio is valuable for risk stratification in patients with sepsis and is associated with poor clinical outcomes for sepsis in the ICU.
裂变蛋白1(Fis1)和帕金蛋白分别是与线粒体裂变和线粒体自噬相关的关键蛋白。本研究旨在评估Fis1/帕金蛋白比值作为脓毒症患者生物标志物的预后价值。在重症监护病房(ICU)入院后24小时内,纳入连续的脓毒症患者(n = 133)或单纯感染患者(n = 24)。在ICU入院时,通过酶联免疫吸附测定(ELISA)测量血清中Fis1、帕金蛋白、线粒体融合蛋白2(Mfn2)和过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)的水平。还收集了临床参数和标准实验室检测数据。所有患者均接受至少28天的随访。脓毒症患者在ICU入院时血清帕金蛋白、Mfn2和PGC-1α水平显著降低,但血清Fis1水平以及Fis1/帕金蛋白、Fis1/Mfn2和Fis1/PGC-1α比值升高。与单纯感染患者相比,脓毒症患者尤其是脓毒症休克患者的这些比值显著升高。Fis1/帕金蛋白比值的受试者工作特征(ROC)曲线下面积大于Fis1、帕金蛋白、Mfn2和PGC-1α水平以及Fis1/Mfn2和Fis1/PGC-1α比值,用于预测脓毒症导致的28天死亡率。在28天随访检查中,所有比值在非存活者中均显著高于存活者。发现Fis1/帕金蛋白比值是脓毒症患者28天死亡率的独立预测因子。Fis1/帕金蛋白比值对脓毒症患者的风险分层有价值,且与ICU中脓毒症患者不良临床结局相关。