Xu Liang, Zhang Weijun, Sun Renhua, Liu Jingquan, Hong Jun, Li Qian, Hu Bangchuan, Gong Fangxiao
Department of Intensive Care Unit, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
Department of Neurology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang 310006, P.R. China.
Exp Ther Med. 2017 Jul;14(1):797-804. doi: 10.3892/etm.2017.4553. Epub 2017 Jun 7.
IGF-1 functions as an anti-oxidative stress molecule and some critical patients with sepsis have a lower level of serum IGF-1. However, the association between IGF-1 and the severity or prognosis of sepsis remains unclear. This study aimed to elucidate the relationship between serum IGF-1 levels and the severity and prognosis of sepsis, and the possible mechanism was analyzed. Clinical characteristics of patients with sepsis were recorded and analyzed. Serum IGF-1 levels and micro (mi)RNA-1 levels were tested using radioimmunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, respectively. The A549 cell line and HKC cell line were cultured and exposed to HO with or without IGF-1 treatment. Cell death was detected by analyzing cell death markers via ELISA kits, and miRNA-1 levels were detected after HO exposure using RT-qPCR analysis. miRNA-1 in cells was upregulated by transfection and IGF-1 mRNA was detected to determine its relationship with miRNA-1. Once again, cell ELISA kits were used to analyze cell death markers after transfection. Serum IGF-1 levels were reduced in patients with sepsis, whereas miRNA-1 levels were higher (P<0.05 vs. healthy control). Patients in the septic shock subgroup or dead patients had the lowest IGF-1 levels and the highest miRNA-1 levels (P<0.05 vs. sepsis and severe sepsis). IGF-1 levels were inversely proportional to the miRNA-1 level. , IGF-1 reduced the cell death caused by HO. miRNA-1 transfection effectively increased the sensitivity of cells to HO damage by reducing the expression of IGF-1, which was able to prevent cells from injury caused by HO. The transfection of negative control miRNA did not influence the level of IGF-1 miRNA and the sensitivity to HO damage. In conclusion, low IGF-1 levels in patients with sepsis may predict increased severity of the condition and poor prognosis. The possible mechanism is that the excessive miRNA-1 levels reduce IGF-1 levels, resulting in insufficient anti-oxidative action by IGF-1 which increases the injury caused by oxidative stress in patients with sepsis.
胰岛素样生长因子-1(IGF-1)作为一种抗氧化应激分子发挥作用,一些重症脓毒症患者血清IGF-1水平较低。然而,IGF-1与脓毒症严重程度或预后之间的关联仍不明确。本研究旨在阐明血清IGF-1水平与脓毒症严重程度及预后的关系,并分析其可能机制。记录并分析脓毒症患者的临床特征。分别采用放射免疫分析法和逆转录定量聚合酶链反应(RT-qPCR)分析检测血清IGF-1水平和微小(mi)RNA-1水平。培养A549细胞系和HKC细胞系,并在有或无IGF-1处理的情况下使其暴露于过氧化氢(HO)。通过酶联免疫吸附测定试剂盒分析细胞死亡标志物来检测细胞死亡情况,并在HO暴露后使用RT-qPCR分析检测miRNA-1水平。通过转染上调细胞中的miRNA-1,并检测IGF-1 mRNA以确定其与miRNA-1的关系。再次使用细胞酶联免疫吸附测定试剂盒分析转染后的细胞死亡标志物。脓毒症患者血清IGF-1水平降低,而miRNA-1水平升高(与健康对照相比,P<0.05)。感染性休克亚组患者或死亡患者的IGF-1水平最低,miRNA-1水平最高(与脓毒症和严重脓毒症相比,P<0.05)。IGF-1水平与miRNA-1水平呈负相关。IGF-1减少了HO引起的细胞死亡。miRNA-1转染通过降低IGF-1的表达有效增加了细胞对HO损伤的敏感性,这能够防止细胞受到HO引起的损伤。阴性对照miRNA的转染不影响IGF-1 miRNA水平及对HO损伤的敏感性。总之,脓毒症患者IGF-1水平低可能预示病情严重程度增加及预后不良。可能的机制是miRNA-1水平过高降低了IGF-1水平,导致IGF-1的抗氧化作用不足,从而增加了脓毒症患者氧化应激引起的损伤。