基于多组学数据整合探讨机械通气相关性肺损伤预警标志物的产生机制

“Coexistence of effects and side effects as same as the treatment and injury”. Although mechanical ventilation can provide effective respiratory support, but it also can lead to lung injury which is closely related to the prognosis. It is one of the most effective methods to reduce the damage through real-time adjustment of treatment parameters according to the early warning markers. Our previous study found that mechanical ventilation can lead to inappropriate metabolic fingerprint in the blood.Then we analyzed the possible mechanisms through integration of metabolomics, proteomics and transcriptomics combined with the immunohistochemical localization. We hypothesized that mechanical ventilation can lead to the up-regulation of NR3C1 expression in lung epithelial cells which mainly affects 2 key metabolic enzymes (GLUL, ABAT) , followed by the "quality" or "quantity" change of metabolic products.Some metabolites released into the blood and then were detected by the instrument.This project will first use animal models to verify the early warning value of metabolites and then use lung epithelial cells under mechanical stretch to investigate the molecular mechanism.This study will provide some theoretical basis for clinical prevention and treatment of lung injury induced by mechanical ventilation.

“作用与副作用同在，治疗与损伤并存”，机械通气虽然可以提供有效的呼吸支持，但同时也会导致肺部损伤，并且这种损伤程度与预后密切相关。早期发现预警标记物，实时调节治疗参数是减轻损伤最有效的方法之一。我们前期采用代谢组学检测发现不恰当的机械通气可以导致血液中出现异常的代谢指纹图谱，而后整合代谢组、蛋白组与转录组三层组学数据分析其产生的原因，结合免疫组化定位，我们推测：机械通气可以引起肺上皮细胞中NR3C1表达上调，致使其调控的两个代谢通路关键酶（GLUL、ABAT）活性/含量改变，继而引发代谢产物“质”和“量”的改变，部分特征性代谢产物在机械力学破坏作用下释放入血，由此血清中出现特征性代谢指纹图谱。本项目将首先采用在体实验验证代谢指纹图谱的预警价值，然后拟结合分子生物学方法，在机械牵拉处理的肺上皮细胞中验证其产生的具体分子机制,为临床防治机械通气相关性肺损伤提供相关理论依据和策略。

机械通气虽然可以提供有效的呼吸支持，但也会导致肺部损伤，并且这种损伤程度与预后密切相关；早期发现预警标记物，实时调节治疗参数是减轻损伤最有效的方法之一。本课题采用代谢组学检测发现不恰当的机械通气可以导致血液中出现异常的代谢指纹图谱，而后整合代谢组、蛋白组与转录组三层数据分析了其产生的原因，并选择临床麻醉和监护室中最为常见具有代表性的三种肺损伤病因作为对照，以此区分了物理性损伤（机械通气损伤）的特异性问题。通过研究发现机械通气可以引起肺组织代谢产物“质”和“量”的改变，部分特征代谢产物在机械力学破坏作用下释放入血，由此血清中出现特征性代谢指纹图谱。本项目采用在体实验验证了代谢图谱的预警价值，然后结合分子生物学方法，在机械牵拉处理的肺上皮细胞中验证了其产生的具体分子机制,为临床防治机械通气相关性肺损伤提供了相关理论依据和策略。