Serine/threonine kinase-protein kinase B and extracellular signal-regulated kinase regulate ventilator-induced pulmonary fibrosis after bleomycin-induced acute lung injury: a prospective, controlled animal experiment.
Serine/threonine kinase-protein kinase B and extracellular signal-regulated kinase regulate ventilator-induced pulmonary fibrosis after bleomycin-induced acute lung injury: a prospective, controlled animal experiment.
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DOI：
10.1186/cc6983
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发表时间：
2008
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;Huang CC;Hung MJ;Quinn DA
急性肺损伤患者的肺纤维化、肺顺应性降低和严重低氧血症往往导致需要机械通气的支持。高潮气量机械通气可增加肺损伤和纤维化活性，但调节高潮气量与肺纤维化相互作用的机制尚不清楚。我们假设高潮气量通气通过丝氨酸/苏氨酸激酶-蛋白激酶B （Akt）和丝裂原激活的蛋白激酶途径增加急性肺损伤的肺纤维化。给博来霉素模拟急性肺损伤5天后，体重20 ~ 25 g的雄性C57BL/6小鼠分别在室内空气中进行高潮气量机械通气（30 ml/kg）或低潮气量机械通气（6 ml/kg） 1 ~ 5小时。高潮气量通气诱导I型和III型前胶原mRNA表达、微血管通透性、羟脯氨酸含量、马松三色染色、S100A4/成纤维细胞特异性蛋白-1染色、Akt和细胞外信号调节激酶（ERK） 1/2的激活、巨噬细胞炎症蛋白-2和10 kDa ifn γ诱导蛋白的产生，均呈剂量依赖性。在akt缺乏小鼠和PD98059药物抑制ERK1/2活性的小鼠中，高潮气量通气诱导的肺纤维化减轻。我们得出结论，大潮气量通气诱导的微血管通透性、肺纤维化和趋化因子的产生部分依赖于Akt和ERK1/2通路的激活。
Lung fibrosis, reduced lung compliance, and severe hypoxemia found in patients with acute lung injury often result in a need for the support of mechanical ventilation. High-tidal-volume mechanical ventilation can increase lung damage and fibrogeneic activity but the mechanisms regulating the interaction between high tidal volume and lung fibrosis are unclear. We hypothesized that high-tidal-volume ventilation increased pulmonary fibrosis in acute lung injury via the serine/threonine kinase-protein kinase B (Akt) and mitogen-activated protein kinase pathways. After 5 days of bleomycin administration to simulate acute lung injury, male C57BL/6 mice, weighing 20 to 25 g, were exposed to either high-tidal-volume mechanical ventilation (30 ml/kg) or low-tidal-volume mechanical ventilation (6 ml/kg) with room air for 1 to 5 hours. High-tidal-volume ventilation induced type I and type III procollagen mRNA expression, microvascular permeability, hydroxyproline content, Masson's trichrome staining, S100A4/fibroblast specific protein-1 staining, activation of Akt and extracellular signal-regulated kinase (ERK) 1/2, and production of macrophage inflammatory protein-2 and 10 kDa IFNγ-inducible protein in a dose-dependent manner. High-tidal-volume ventilation-induced lung fibrosis was attenuated in Akt-deficient mice and in mice with pharmacologic inhibition of ERK1/2 activity by PD98059. We conclude that high-tidal-volume ventilation-induced microvascular permeability, lung fibrosis, and chemokine production were dependent, in part, on activation of the Akt and ERK1/2 pathways.
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影响因子：
5.8
作者：
Failla M;Genovese T;Mazzon E;Gili E;Muià C;Sortino M;Crimi N;Caputi AP;Cuzzocrea S;Vancheri C
通讯作者：
Vancheri C
DOI：
10.1165/rcmb.2002-0167oc
发表时间：
2004-01-01
影响因子：
6.4
作者：
Mascarenhas, MM;Day, RM;Quinn, DA
通讯作者：
Quinn, DA
影响因子：
4.4
作者：
Cara, DC;Kaur, J;Kubes, P
通讯作者：
Kubes, P
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：
15.1
作者：
de Carvalho, Maria-Eudoxia Pilotto;Dolhnikoff, Marisa;Deheinzelin, Daniel
通讯作者：
Deheinzelin, Daniel