p38 MAPK抑制剂对急性肺损伤的治疗作用

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(ALI)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1 h后P_(A-a)O_2、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,P_(A-a)O_2、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.

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

Objective To evaluate the effects and mechanisms of p38 MAPK inhibitor on animal model of endotoxin-induced lung injury. Methods The rabbit ALI model was established by intravenous injection with LPS; blood gas analysis, serum tumor necrosis factor α (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 P_(A-a)O_2, 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, P_(A-a)O_2, 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 ALI in rabbits may be as: alleviating hypoxemia, lung edema and inflammatory reaction, and improving histopathology performance.