p38 MAPK抑制剂对急性肺损伤的治疗作用

Therapeutic effects of p38 MAPK inhibitor on acute lung injury in rabbits

目的观察p38丝裂原活化蛋白激酶（MAPK）抑制剂SB203580对LPS诱导的兔急性肺损伤（ALl）的保护作用及其机制。方法用大肠杆菌内毒素（LPS）制备兔ALI模型；测定不同时间点的动脉血气分析、血清TNF—α和ICAM-1浓度；测量肺干／湿质量比值（肺D／W）及观察肺组织病理学改变。结果动物注射内毒素1h后PA-aO2、血浆TNF—α和ICAM-1水平、肺损伤评分均明显升高（P〈0．05），肺D／W下降（P〈0．05）；应用SB203580治疗后，PA-aO2、血浆TNF—α和ICAM-1水平、肺损伤评分均明显下降（P〈0．05），肺D／W升高（P〈0．05）。结论本研究结果表明，p38 MAPK抑制剂SB203580对内毒素诱导的ALI，可以明显减轻低氧血症、减轻肺水肿、改善组织病理学和减轻炎症反应。

Objective To evaluate the effects and mechanisms of p38 MAPK inhibitor on animal model of endotoxin - induced lung injury. Methods The rabbit ALl model was established by intravenous injection with LPS; blood gas analysis, serum tumor necrosis factor ot （TNF - α ） and intercellular adhesion molecule 1 （ ICAM - 1 ） levels were measured ; the ratio of dry weight and wet weight （D/W） of the lung was calculated, and lung histopathologic changes were observed. Results PA-aO2, serum TNF - α and ICAM - 1 levels, the lung injury score increased and lung D/W decreased after LPS injection（ P 〈 0. 05 ）. After the administration of p38 MAPK inhibitor, SB203580, PA -aO2, serum TNF - α and ICAM - 1 levels, the lung injury score decreased and lung D/W increased （ P 〈 0. 05）. Conclusion The therapeutic effects of SB203580 on ALl in rabbits may be as： alleviating hypoxemia, lung edema and inflammatory reaction, and improving histopathology performance.