Shaoxing Second Hospital, 123 Yanan Road, Shaoxing, Zhejiang 312000, China.
Tongde Hospital of Zhejiang, 132 Tianmushan Road, Hangzhou, Zhejiang 310007, China.
Mediators Inflamm. 2020 Jan 22;2020:4370983. doi: 10.1155/2020/4370983. eCollection 2020.
Recent literature has reported the use of circulating microRNAs (miRNAs) as biomarkers for sepsis. Immune cells play an essential role in the pathophysiology of sepsis. The aim of this prospective study was to identify miRNAs in peripheral blood mononuclear cells (PBMC) that could differentiate between sepsis and infection based on Sepsis-3 definition.
A total of 62 patients (41 with sepsis and 21 with infection suffering from pneumonia but without sepsis) and 20 healthy controls were enrolled into the study. PBMC at admission were examined for a panel of 4 miRNAs (miR-10a, miR-17, miR-27a, and miR-125b), which have been documented to participate in inflammatory response in immune cells, via qRT-PCR. Data were validated in a mouse model of sepsis induced via cecal ligation and puncture (CLP) and THP-1 monocytes.
miR-10a levels in PBMC at admission were significantly lower in sepsis patients compared with patients with infection and healthy controls. miR-10a levels were negatively correlated with disease severity scores as well as levels for c-reactive protein and procalcitonin. In addition, low miR-10a expression had a diagnostic value for sepsis and a prognostic value for 28-day mortality in receiving operating characteristic analysis. Compared with infection patients and healthy controls, PBMC from sepsis patients also had higher levels of mitogen-activated kinase kinase kinase 7 (MAP3K7), a known target protein of miR-10a and an activator of the NF-B pathway. In the mouse model of CLP-induced sepsis, miR-10a levels in PBMC were significantly decreased as early as 8 h after CLP. Overexpression of miR-10a in THP-1 cells significantly reduced the expression of MAP3K7 and proinflammatory cytokines including IL-6, TNF-, and MCP-1.
PBMC miR-10a levels are decreased in sepsis and negatively correlated with the disease severity. Levels of miR-10a could distinguish between sepsis and infection and predict 28-day mortality. miR-10a plays an anti-inflammatory role in the pathogenesis of sepsis.
最近的文献报道了循环 microRNAs（miRNAs）作为脓毒症生物标志物的应用。免疫细胞在脓毒症的病理生理学中起着至关重要的作用。本前瞻性研究的目的是鉴定外周血单个核细胞（PBMC）中的 miRNAs，这些 miRNAs 可以根据 Sepsis-3 定义区分脓毒症和感染。
共纳入 62 例患者（41 例脓毒症和 21 例肺炎感染但无脓毒症）和 20 名健康对照者。入院时通过 qRT-PCR 检测 PBMC 中一组 4 种 miRNAs（miR-10a、miR-17、miR-27a 和 miR-125b）的表达，这些 miRNAs 已被证明参与免疫细胞中的炎症反应。研究数据在盲肠结扎和穿刺（CLP）诱导的脓毒症小鼠模型和 THP-1 单核细胞中进行了验证。
与感染患者和健康对照者相比，脓毒症患者入院时 PBMC 中的 miR-10a 水平显著降低。miR-10a 水平与疾病严重程度评分以及 C 反应蛋白和降钙素原水平呈负相关。此外，在接受操作特征分析时，低 miR-10a 表达对脓毒症具有诊断价值，对 28 天死亡率具有预后价值。与感染患者和健康对照者相比，脓毒症患者的 PBMC 中丝裂原激活蛋白激酶激酶激酶 7（MAP3K7）水平也较高，MAP3K7 是 miR-10a 的已知靶蛋白，也是 NF-B 通路的激活剂。在 CLP 诱导的脓毒症小鼠模型中，CLP 后 8 小时 PBMC 中的 miR-10a 水平即明显降低。在 THP-1 细胞中过表达 miR-10a 可显著降低 MAP3K7 和包括白细胞介素 6（IL-6）、肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白-1（MCP-1）在内的促炎细胞因子的表达。
脓毒症患者 PBMC miR-10a 水平降低，与疾病严重程度呈负相关。miR-10a 水平可区分脓毒症和感染，并预测 28 天死亡率。miR-10a 在脓毒症发病机制中发挥抗炎作用。
