Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury
Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury
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DOI：
10.1016/j.pupt.2007.03.001
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发表时间：
2008-01-01
影响因子：
3.2
通讯作者：
Carbognani, Paolo
中科院分区：
文献类型：
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作者：
Bertorelli, Giuseppina;Pesci, Alberto;Carbognani, Paolo
背景和目标：急性呼吸窘迫综合征（ARDS）是一种常见的低氧血症性呼吸衰竭，由弥漫性肺部炎症急性发展引起。全身炎症反应失调和循环炎性细胞因子持续升高是ARDS患者肺及肺外器官功能障碍的发病机制。糖皮质激素（GC）具有广泛的抑制炎症作用，包括抑制细胞因子转录、细胞活化和生长因子产生。它们通过两种特异性细胞内糖皮质激素受体（GR）（称为GR α和GR β）抑制炎症途径。本研究的目的是评价急性肺损伤（acutelunginjury，ALI）不同实验模型中炎性损伤的组织学证据以及驻留细胞和炎性细胞摄取GR α的情况。ALI是由气压伤（由于过度通气）、油酸注射和机械通气引起的。结果与非通气大鼠对照组进行比较。机械通气时间为2.5 h。在每个实验结束时，处死大鼠。评估肺活检的形态学变化。结果：所有机械通气组均出现肺损伤（肺泡和间质水肿、血管充血、肺泡出血、肺气肿、间质细胞和中性粒细胞数量增加、肺泡附着物破坏）。气压伤导致额外的炎症反应。与非通气组相比，三个通气组中GR α表达显著增加。结论：ALI与弥漫性肺泡损伤、炎症反应上调及GR α过度表达有关。气压伤是引起急性肺部炎症和GR α过度表达的最有效机制。(c)2007爱思唯尔有限公司保留所有权利。
Background and objectives: Acute respiratory distress syndrome (ARDS) is a frequent form of hypoxiemic respiratory failure caused by the acute development of diffuse lung inflammation. Dysregulated systemic inflammation with persistent elevation of circulating inflammatory cytokines is the pathogenetic mechanism for pulmonary and extrapulmonary organ dysfunction in patients with ARDS. Glucocorticoids (GCs) have a broad range of inhibitory inflammatory effects, including inhibition of cytokines transcription, cellular activation and growth factor production. They inhibit the inflammatory pathways through two specific intracellular glucocorticoid receptors (GRs), named GR alpha and GR beta. The aim Of Our study was to evaluate the histologic evidence of inflammatory injury and the GRa uptake of resident and inflammatory cells in different experimental models of acute lung injury (ALI).Methods: We studied four groups of rats: three different experimental rat models of lung injury and a control group. The ALI was caused by barotrauma (due to an overventilation), oleic acid injection and mechanical ventilation. Results were compared to nonventilated rat control group. The duration of mechanical ventilation was of 2.5 h. At the end of each experiment, rats were sacrificed. Lung biopsies were evaluated for morphologic changes. The immunohistochemistry was performed to Study GR alpha expression.Results: Histologic evidence Of lung injury (alveolar and interstitial edema, vascular congestion, alveolar haemorrhage, emphysema, number of interstitial cells and neutrophils, and destruction of alveolar attachments) were present in all ventilated groups. Barotrauma lead to an additional inflammatory response. GR alpha expression significantly increased in the three ventilated groups compared with nonventilated groups. GR alpha expression was highest in barotrauma group.Conclusions: These data indicate that ALI is associated with diffuse alveolar damage, up-regulation of the inflammatory response and GR alpha overexpression. Barotrauma is the most effective mechanism inducing acute lung inflammation and GR alpha overexpression. (c) 2007 Elsevier Ltd. All rights reserved.