Hyperoxia increases ventilator-induced lung injury via mitogen-activated protein kinases: a prospective, controlled animal experiment.
Hyperoxia increases ventilator-induced lung injury via mitogen-activated protein kinases: a prospective, controlled animal experiment.
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高氧通过促丝分裂原激活的蛋白激酶增加了呼吸机诱导的肺损伤：一种前瞻性，受控的动物实验。
DOI：
10.1186/cc5704
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Quinn DA
中科院分区：
文献类型：
--
作者：
Li LF;Liao SK;Ko YS;Lee CH;Quinn DA
急性呼吸窘迫综合征患者采用大潮气量机械通气和高氧可通过肺部炎症和凋亡细胞死亡损害肺上皮细胞。高氧已被证明会增加呼吸机诱导的肺损伤，但调节大VT和高氧之间相互作用的机制尚不清楚。我们假设在大vt通气中加入高氧会通过上调细胞因子巨噬细胞炎症蛋白-2 （MIP-2）来增加中性粒细胞的浸润，并通过丝裂原激活的蛋白激酶途径增加细胞凋亡。C57BL/6小鼠高vt （30 ml/kg）机械通气1 ~ 5小时，加室内空气或高氧。高室速通气的高氧增加了肺损伤，如凋亡细胞死亡增加，中性粒细胞向肺迁移，MIP-2产生，MIP-2 mRNA表达，激活蛋白-1的DNA结合活性增加，微血管通透性增加，c-Jun nh2末端激酶（JNK）和细胞外信号调节激酶（ERK） 1/2活化。在jnk缺陷小鼠和PD98059药物抑制ERK活性的小鼠中，高氧诱导的高vt诱导的肺损伤增强被减弱。然而，只有jnk缺陷小鼠，而不是PD98059抑制ERK活性的小鼠，在没有高氧的情况下免受高vt诱导的肺损伤。我们得出结论，高氧通过激活JNK和ERK1/2通路，增加了高vt诱导的细胞因子产生、中性粒细胞内流和凋亡细胞死亡。
Large-tidal volume (VT) mechanical ventilation and hyperoxia used in patients with acute respiratory distress syndrome can damage pulmonary epithelial cells through lung inflammation and apoptotic cell death. Hyperoxia has been shown to increase ventilator-induced lung injury, but the mechanisms regulating interaction between large VT and hyperoxia are unclear. We hypothesized that the addition of hyperoxia to large-VT ventilation would increase neutrophil infiltration by upregulation of the cytokine macrophage inflammatory protein-2 (MIP-2) and would increase apoptosis via the mitogen-activated protein kinase pathways. C57BL/6 mice were exposed to high-VT (30 ml/kg) mechanical ventilation with room air or hyperoxia for one to five hours. The addition of hyperoxia to high-VT ventilation augmented lung injury, as demonstrated by increased apoptotic cell death, neutrophil migration into the lung, MIP-2 production, MIP-2 mRNA expression, increased DNA binding activity of activator protein-1, increased microvascular permeability, and c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) 1/2 activation. Hyperoxia-induced augmentation of high-VT-induced lung injury was attenuated in JNK-deficient mice and in mice with pharmacologic inhibition of ERK activity by PD98059. However, only JNK-deficient mice, and not mice with ERK activity inhibition by PD98059, were protected from high-VT-induced lung injury without hyperoxia. We conclude that hyperoxia increased high-VT-induced cytokine production, neutrophil influx, and apoptotic cell death through activation of the JNK and ERK1/2 pathways.
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DOI：
10.1165/ajrcmb.19.4.3173
发表时间：
1998-10-01
影响因子：
6.4
作者：
Barazzone, C;Horowitz, S;Piguet, PF
通讯作者：
Piguet, PF
影响因子：
7.4
作者：
Franek, WR;Morrow, DMP;Mantell, UL
通讯作者：
Mantell, UL
DOI：
10.1152/ajplung.00031.2003
发表时间：
2003-08-01
影响因子：
4.9
作者：
Li, LF;Ouyang, B;Quinn, DA
通讯作者：
Quinn, DA
DOI：
10.1164/ajrccm.163.3.2003001
发表时间：
2001-03-01
影响因子：
24.7
作者：
Held, HD;Boettcher, S;Uhlig, S
通讯作者：
Uhlig, S
影响因子：
7.4
作者：
Romashko, J;Horowitz, S;Mantell, LL
通讯作者：
Mantell, LL