Role of extracellular signal-regulated protein kinase (ERK) in 17β-estradiol-mediated attenuation of lung injury after trauma-hemorrhage
Role of extracellular signal-regulated protein kinase (ERK) in 17β-estradiol-mediated attenuation of lung injury after trauma-hemorrhage
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DOI：
10.1016/j.surg.2008.10.008
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发表时间：
2009-02-01
期刊：
影响因子：
3.8
通讯作者：
Chaudry, Irshad H.
中科院分区：
文献类型：
--
作者：
Hsu, Jun-Te;Kan, Wen-Hong;Chaudry, Irshad H.
背景细胞外信号调节蛋白激酶（ERK）参与了细胞损伤后的促炎和趋化反应。本研究的目的是阐明ERK是否在17 β-雌二醇（E2）介导的减轻创伤后肺损伤和促炎介质中发挥任何作用。雄性Sprague-Dawley大鼠经历创伤-出血（平均血压类似于40 mm Hg持续90分钟），随后进行液体复苏。在复苏开始时，用媒介物（环糊精）、E2（1 mg/kg体重[BW]）或ERK抑制剂PD 98059（2 mg/kg BW）处理大鼠。于假手术或创伤出血后2 h测定各项指标。创伤出血导致肺ERK磷酸化显著增加，这与肺髓过氧化物酶活性、湿干重比、白细胞介素（IL）-6、肿瘤坏死因子（达特）-α、细胞间粘附分子（ICAM）-1、嘌呤诱导的中性粒细胞趋化因子（CINC）-1和巨噬细胞炎性蛋白-2水平增加相关。与假手术组相比，创伤出血后循环中IL-6、TNF-α和乳酸水平也增加。创伤失血后给予E2或ERK抑制剂PD 98059可减轻创伤失血引起的肺损伤标志物、ERK磷酸化、细胞因子/趋化因子、ICAM-1产生以及循环细胞因子和乳酸水平的升高。这些结果共同表明，创伤出血后E2对肺的有益作用是通过ERK途径介导的，随后下调促炎介质的产生。（《外科学》2009年，145：226- 234。）
Background. Extracellular signal-regulated protein kinase (ERK) is known to be involved in proinflammatory and chemotactic events in response to injury. The aim of this study is to elucidate whether ERK plays any role in 17 beta-estradiol (E2)-mediated attenuation of lung injury and pro-inflammatory mediators after trauma-hemorrhage.Methods. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure similar to 40 mm Hg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle (cyclodextrin), E2 (1 mg/kg body weight [BW]), or the ERK inhibitor PD98059 (2 mg/kg BW). At 2 h after sham operation or trauma-hemorrhage, various parameters were measured.Results. Trauma-hemorrhage led to a significant increase in lung ERK phosphorylation, which was associated with increased lung myeloperoxidase activity, wet-to-dry weight ratio, interleukin (IL)-6, tumor necrosis factor (TAT)-alpha, intercellular adhesion molecule (ICAM)-1, cytokine-induced neutrophil chemoattractant (CINC)-1, and macrophage inflammatory protein-2 levels. Circulatory IL-6, TNF-alpha, and lactate levels were also increased after trauma-hemorrhage compared with shams. Administration Of E2 or ERK inhibitor PD98059 after trauma-hemorrhage attenuated the trauma-hemorrhage-induced increase in lung injury markers, ERK phosphorylation and cytokines/chemokines, ICAM-1 production, (is well as circulatory cytokines and lactate levels.Conclusion. These results collectively suggest that the salutary effects of E2 on the lung after trauma-hemorrhage are mediated via an ERK pathway and subsequent downregulation of pro-inflammatory mediator production. (Surgery 2009,145:226-34.)