p38丝裂原活化蛋白激酶在大鼠油酸型急性肺损伤中的作用

doi:10.12047/j.cjap.5552.2017.081

中国应用生理学杂志 ›› 2017, Vol. 33 ›› Issue (4): 334-339.doi: 10.12047/j.cjap.5552.2017.081

p38丝裂原活化蛋白激酶在大鼠油酸型急性肺损伤中的作用

黄斌¹, 邓旺², 王导新²

1. 重庆医科大学附属第二医院重症医学科, 重庆 400010;
2. 重庆医科大学附属第二医院呼吸内科, 重庆 400010

收稿日期:2017-01-11 修回日期:2017-05-12 出版日期:2017-07-28 发布日期:2018-06-19
通讯作者: 王导新,Tel:023-63693093;E-mail:wangdaoxincq@yeah.net E-mail:wangdaoxincq@yeah.net
基金资助:
重庆市卫生局2009年度医学科研计划项目（2009-2-165）；国家自然科学基金资助课题（81270141）

Effects of p38 mitogen-activated protein kinase in rats with oleic acid-induced acute lung injury

HUANG Bin¹, DENG Wang², WANG Dao-xin²

1. Department of Critical Care Medicine of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010;
2. Department of Respiratory Medicine of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China

Received:2017-01-11 Revised:2017-05-12 Online:2017-07-28 Published:2018-06-19
Supported by:
重庆市卫生局2009年度医学科研计划项目（2009-2-165）；国家自然科学基金资助课题（81270141）

摘要/Abstract

摘要： 目的：研究p38丝裂原活化蛋白激酶（p38MAPK）通路抑制剂SB203580对油酸性急性肺损伤（ALI）大鼠炎症反应及肺水清除的影响，探讨油酸性急性肺损伤中p38MAPK的作用机制，为p38MAPK抑制剂SB203580干预脂肪栓塞综合征诱导肺损伤提供新途径。方法：24只SD雄性成年大鼠随机分为对照组（8只）、油酸模型组（8只）和SB203580干预组（8只）。油酸模型组大鼠经右颈静脉注射油酸0.20 ml/kg，造成急性肺损伤模型；SB203580组大鼠在油酸造模前30 min静脉注射SB203580；建模4 h后处死动物，检测血气分析、右下肺湿干重比（W/D）、肺系数（LI）、肺通透指数（PPI），ELISA法检测支气管肺泡灌洗液（BALF）中TNF-α含量，免疫组化和Western blot法检测肺组织p38MAPK、p-p38MAPK蛋白表达水平，检测肺组织病理变化。结果：与对照组相比，油酸模型组大鼠PaO₂及PaO₂/FiO₂明显降低，右下肺湿干重、肺系数和肺通透指数、BALF中炎症因子TNF-α的含量以及p-p38MAPK蛋白表达均明显增加（P<0.01），肺组织病理学显示明显的急性肺损伤；与油酸模型组相比，以上指标在SB203580干预组则明显改善（P<0.01）。结论：p38MAPK信号通路介导的炎性反应在油酸性肺损伤的发病机制中具有重要作用，p38MAPK抑制剂SB203580显著抑制炎症因子的表达，减轻肺水肿，对油酸性肺损伤具有明显的肺保护作用，意味着对p38MAPK的抑制可望为临床上伴有脂肪栓塞综合征（FES）的ALI的防治提供新途径。

关键词: 急性肺损伤, p38丝裂原活化蛋白激酶, 炎性反应, 油酸

Abstract: Objective: To study the effects of p38 mitogen-activated protein kinase (p38MAPK) signal transduction pathway inhibitor SB203580 on the inflammatory reaction and lung water clearance, and to explore the role of p38MAPK in acute lung injury, to provide new way for p38MAPK inhibitor -SB203580 intervene fat embolism syndrome induced lung injury.Methods: Twenty-four adult male SD rats were randomly assigned to normal control group (OA group) (n=8), oleic acid-induced lung injury group (OA group, n=8)and SB203580 pretreatment group (n=8). OA-group was administered oleic acid (0.20 ml/kg) via right jugular vein; In SB203580-group, SB203580(5 mg/kg) was injected via jugular vein, followed 30 min before by OA infusion; At the 4 hours animals were sacrificed. Arterial blood gas, the wet/dry weight(W/D)of the right lower lung were examined, lung index(LI), pulmonary permeability index(PPI) and levels of tumor necrosis factor α(TNF-α) in bronchoalveolar lavage fluid(BALF) were examined. The expressions of p38MAPK and phospho-p38MAPK (p-p38MAPK) were determined by Western blot and immunohistochemical method. Pathological changes of the lung tissue were examined with light microscrope.Results: Compared to control group, arterial oxygen partial pressure (PaO₂) and PaO₂/FiO₂ were decreased in the animals of OA-group, while right lower lung wet/dry ratio, lung index, PPI, levels of TNF-α in BALF and the protein expression of p-p38MAPK were increased significantly (P<0.01). The pathological changes were observed significantly in injured lung tissue. Compared to OA-group, those indexes were improved in SB203580 pretreated group.Conclusion: p38MAPK signal transaction path mediated inflammatory response process and played an important role in acute lung injury. SB203580 could inhibit the expression of inflammatory cytokines, reduce lung edema, protect lung tissue of rats from OA-induced lung injury obviously. Therefore, inhibition of p38MAPK activity provides a new way for the clinical treatment of fat embolism syndrome induced lung injury.

Key words: acute lung injury, p38MAPK, inflammatory reaction, oleic acid

黄斌, 邓旺, 王导新. p38丝裂原活化蛋白激酶在大鼠油酸型急性肺损伤中的作用[J]. 中国应用生理学杂志, 2017, 33(4): 334-339.

HUANG Bin, DENG Wang, WANG Dao-xin. Effects of p38 mitogen-activated protein kinase in rats with oleic acid-induced acute lung injury[J]. CJAP, 2017, 33(4): 334-339.

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p38丝裂原活化蛋白激酶在大鼠油酸型急性肺损伤中的作用

Effects of p38 mitogen-activated protein kinase in rats with oleic acid-induced acute lung injury

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