Huang Bin, Deng Wang, Wang Dao-Xin
Department of Critical Care Medicine of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010.
Department of Respiratory Medicine of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2017 Apr 8;33(4):334-339. doi: 10.12047/j.cjap.5552.2017.081.
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.
Twenty-four adult male SD rats were randomly assigned to normal control group (OA group) (=8), oleic acid-induced lung injury group (OA group, =8)and SB203580 pretreatment group (=8). OA-group was administered oleic acid (0.20 ml/kg) right jugular vein; In SB203580-group, SB203580(5 mg/kg) was injected 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.
Compared to control group, arterial oxygen partial pressure (PaO) and PaO/FiO 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 (<0.01). The pathological changes were observed significantly in injured lung tissue. Compared to OA-group, those indexes were improved in SB203580 pretreated group.
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.
研究p38丝裂原活化蛋白激酶（p38MAPK）信号转导通路抑制剂SB203580对炎症反应及肺水清除的影响，探讨p38MAPK在急性肺损伤中的作用，为p38MAPK抑制剂-SB203580干预脂肪栓塞综合征所致肺损伤提供新途径。
将24只成年雄性SD大鼠随机分为正常对照组（OA组，n=8）、油酸诱导的肺损伤组（OA组，n=8）和SB203580预处理组（n=8）。OA组经右颈静脉注射油酸（0.20 ml/kg）；SB203580组经颈静脉注射SB203580（5 mg/kg），30分钟后输注油酸；4小时后处死动物。检测动脉血气、右下肺湿/干重（W/D），计算肺指数（LI）、肺通透指数（PPI），检测支气管肺泡灌洗液（BALF）中肿瘤坏死因子α（TNF-α）水平。采用蛋白质印迹法和免疫组织化学法检测p38MAPK和磷酸化p38MAPK（p-p38MAPK）的表达。用光学显微镜观察肺组织病理变化。
与对照组相比，OA组动物动脉血氧分压（PaO₂）和PaO₂/FiO₂降低，右下肺湿/干比、肺指数、PPI、BALF中TNF-α水平及p-p38MAPK蛋白表达显著升高（P<0.01）。损伤肺组织有明显病理变化。与OA组相比SB203580预处理组上述指标有所改善。
p38MAPK信号转导通路介导炎症反应过程，在急性肺损伤中起重要作用。SB203580可抑制炎性细胞因子表达，减轻肺水肿，明显保护大鼠肺组织免受油酸所致肺损伤。因此，抑制p38MAPK活性为脂肪栓塞综合征所致肺损伤的临床治疗提供了新途径。
