Ding Haoshu, Wang Yan, Dong Wenwen, Ren Rongrong, Mao Yanfei, Deng Xiaoming
Faculty of Anesthesiology, Changhai Hospital Affiliated to Second Military Medical University.
Department of Anesthesiology and Critical Care Medicine, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.
Chem Pharm Bull (Tokyo). 2018;66(7):691-700. doi: 10.1248/cpb.c17-00844.
Ventilator-induced lung injury (VILI) has implications for mortality from acute lung injury (ALI) and for acute respiratory distress syndrome (ARDS) patients; the complicated mechanisms of VILI have not been well defined. To discover new biomarkers and mechanisms of VILI, isobaric Tag for Relative and Absolute Quantitation (iTRAQ)-based quantitative proteomics were applied to identify differentially expressed proteins in mice treated with high tidal volume ventilation (HV), low tidal volume ventilation (LV) and lipopolysaccharide (LPS). A total of 14 dysregulated proteins showed the same change trend both in the LV and HV group and no change in the LPS group, and most importantly, the fold change of these proteins increased with the increase of volume ventilation, which indicates these proteins may be considered as potential markers specific for VILI. Ingenuity pathway analysis (IPA) canonical pathways analysis identified the top 4 canonical pathways, including the extrinsic prothrombin activation pathway, coagulation systems, the intrinsic prothrombin activation pathway and the acute phase response, suggesting that these pathways, as associated with these proteins' expression, may be important therapeutic targets for reducing VILI. These findings will provide a new perspective for understanding the pathogenesis of VILI in the future.
机械通气诱导的肺损伤（VILI）与急性肺损伤（ALI）导致的死亡率以及急性呼吸窘迫综合征（ARDS）患者相关；VILI的复杂机制尚未完全明确。为了发现VILI的新生物标志物和机制，采用基于相对和绝对定量等压标签（iTRAQ）的定量蛋白质组学方法，以鉴定接受高潮气量通气（HV）、低潮气量通气（LV）和脂多糖（LPS）处理的小鼠中差异表达的蛋白质。共有14种失调蛋白在LV组和HV组中呈现相同的变化趋势，而在LPS组中无变化，最重要的是，这些蛋白质的倍数变化随着通气量的增加而增加，这表明这些蛋白质可被视为VILI的潜在特异性标志物。 Ingenuity通路分析（IPA）的经典通路分析确定了前4条经典通路，包括外源性凝血酶原激活途径、凝血系统、内源性凝血酶原激活途径和急性期反应，这表明与这些蛋白质表达相关的这些通路可能是减轻VILI的重要治疗靶点。这些发现将为未来理解VILI的发病机制提供新的视角。
