中文摘要：

目的评价沐舒坦预处理对大鼠机械通气所致肺损伤时p38丝裂原活化蛋白激酶通路（p38MAPK）的影响。方法清洁级健康雄性成年SD大鼠30只，体质量280～320g。采用随机数字表法分为三组（n=10）：对照组（C组）、机械通气肺损伤组（VILI组）和机械通气肺损伤＋沐舒坦预处理组（AMB组）。采用潮气量40mL／kg机械通气4h的方法制备大鼠机械通气肺损伤模型。AMB组予以沐舒坦50mg／kg腹腔注射预处理3d，C组和VILI组给予等容量生理盐水腹腔注射。通气结束后观测各组动脉血氧分压与肺组织病理学结果并进行肺损伤评分，收集支气管肺泡灌洗液（BALF），测定BALF总蛋白、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF—α）、白细胞介素-6（IL-6）和细胞间黏附分子-1（ICAM-1）；取肺组织称质量，计算肺湿／干质量比（W／D），检测磷酸化P—p38MAPK、IL-1βmRNA、TNF—dmRNA、IL-6mRNA和ICAM-1mRNA表达水平。结果与C组比较，VILI组和AMB组肺动脉血氧分压（PaO2）明显降低，W／D、肺损伤评分、BALF总蛋白、IL-1β、TNF—α、IL-6及ICAM-1的浓度，肺组织P—p38 MAPK与IL-1β、TNF—α、IL-6和ICAM-1的mRNA表达水平升高（P〈0．05）；与VILI组比较，AMB组PaO2明显升高，肺W／D、肺损伤评分、BALF总蛋白、IL-1β、TNF—α、IL-6及ICAM-1的浓度，肺组织P—p38MAPK与IL-1β、TNF—α、IL-6和ICAM-1的mRNA表达水平降低（P〈0．05）。结论沐舒坦可减轻大鼠机械通气肺损伤，其机制可能与抑制p38MAPK有关。

英文摘要：

Objective To evaluate the effect of ambroxol on p38 mitogen - activated protein kinase pathway in mice with ventilator - induced lung injury（VILI）. Methods Thirty male SD mice, weighing 280 -320 g, were equally and randomly divided into 3 groups （n = 10 each） using a random number table ： control group （ group C ） , ventilator - induced lung injury group （ group VILI ） , and ventilatorinduced lung injury ＋ ambroxol group （group AMB）. VILI was induced by 4 h mechanical ventilation with tidal volume 40 mL/kg. Ambroxol 50 mg/kg preconditioning was injected intraperitoneally for 3 days in group AMB, while the equal volume of normal saline was given in C and VIL[ groups. The mice were then sacrificed, the arterial blood gas was detected, and broncho - alveolar lavage fluid （BALF） was collected for determination of the concentrations of total protein, interleukin- 1β （ IL - 1 β ） , tumor necrosis factor - α（ TNF - α ） , IL - 6 and intercellular adhesion moleeule - 1 （ ICAM - 1 ）. The lung tissues were removed for determination of wet to dry lung weight ratio （ W/D ratio）, expression of p -p38 MAPK, IL - 1β mRNA, TNF - α mRNA, IL -6 mRNA and ICAM - 1 mRNA, and for examination of the pathological changes which were scored. Results Compared with group C, partial pressure of oxygen in arterial blood （ PaO2 ） was decreased （ P 〈 0.05 ） , W/D ratio, lung injury score, concentrations of total protein, IL - 1β, TNF - α, IL -6 and ICAM - 1 in BALF, and expression of p - p38 MAPK, IL - 1β, TNF - α, IL - 6 and ICAM - 1 mRNA were significantly increased in VILI and AMB groups （P 〈 0.05 ）. Compared with group VILI, PaO2 was increased （P 〈 0.05） , W/D ratio, lung injury score, concentrations of total protein, IL - 113, TNF - α, IL - 6 and ICAM - 1 in BALF, and expression of p - p38 MAPK, IL - 1β, TNF - α, IL - 6 and ICAM - 1 mRNA were decreased in group AMB （P 〈 0.05 ）. Conclusion Ambroxol can attenuate VILI probably through inhibiting p38 mitogen -