沐舒坦预处理对大鼠急性肺损伤的肺保护作用研究

目的：研究不同剂量沐舒坦对大鼠急性肺损伤（ALI）的肺保护作用。方法：将40只SD大鼠随机分成5组，每组8只：生理盐水组（吸入生理盐水）、稀盐酸组（吸入稀盐酸）、稀盐酸吸入＋沐舒坦低剂量处理组吸入稀盐酸＋沐舒坦（10mg·kg^-1·d^-1）]、稀盐酸吸入＋沐舒坦中剂量处理组吸入稀盐酸＋沐舒坦（20mg·kg^-1·d^-1）]、稀盐酸吸入＋沐舒坦高剂量处理组吸入稀盐酸＋沐舒坦（40mg·kg^-1·d^-1）]。稀盐酸吸入4-沐舒坦低、中、高剂量处理组分别予相应剂量沐舒坦行尾静脉注射，生理盐水及稀盐酸组予等体积的生理盐水行尾静脉注射，每天1次，连续3d。在第3天尾静脉注射沐舒坦或生理盐水30min后，生理盐水组以1．2ml·kg^-1生理盐水经气管注入，制作假盐酸吸入急性肺损伤模型作为对照；稀盐酸组、稀盐酸吸入＋沐舒坦低、中、高剂量处理组则以1．2ml·kg“稀盐酸（pH=1．2）行气管内注入，制作盐酸吸入急性肺损伤模型。大鼠建模6h后查动脉血气，测肺湿干重比（W／D），光镜下观察肺组织病理改变，测血清TNF-α、IL-10水平。结果：（1）光镜下组织病理学观察发现，生理盐水组肺损伤最轻，稀盐酸组肺损伤最严重，稀盐酸吸入＋沐舒坦低、中、高剂量处理组的肺损伤介于生理盐水组和稀盐酸组之间，且肺损伤程度与沐舒坦剂量呈负相关；（2）与生理盐水组相比：稀盐酸组，稀盐酸吸入＋沐舒坦低、中、高剂量处理组大鼠肺W／D值、血清TNF-α、IL-10水平明显增高（均P〈0．05），PaO2明显下降（均P〈0．05）；PaCO2稀盐酸组明显增高（P〈0．05），稀盐酸吸入＋沐舒坦低、中、高剂量处理组则无明显差异（P〉0．05）；（3）稀盐酸吸入＋沐舒坦低、中、高剂量处理组与稀盐酸组相比，肺W／D值、PaC02、血清中TNF-α明显下降（均P〈0．05），PaO2、血?

Observation of protective effect of Ambroxol against Hcl-induced acute lung injury in rats

Objective： To investigate the protective effect of different dose of Ambroxol against Hcl-induced acutelung injury in rats. Methods： Fouty pathogen-free SD rats were randomly divided into five groups： saline group （ n = 8 ） ： （ saline inhalation）, Hcl group （ n = 8 ） （ Hcl inhalation）, Hcl with low-dose of Ambroxol treatment group （ n = 8） Hcl inhalation ＋ Ambroxol （ 10 mg· kg^-1 · d ^-1 ） ], Hcl with middle- dose of Ambroxol treatment group （ n = 8 ） Hcl inhalation ＋ Ambroxol （20 mg · kg^-1· d ^-1 ） ], Hcl with high- dose of Ambroxol treatment group （ n = 8） Hcl inhalation ＋ Ambroxol （40 mg · kg^-1· d^-1 ）]; Treatment groups were respectively injected with corresponding dosage of Ambroxol, saline group and Hcl group with normal saline, once a day for 3 consecutive days. On the third day, rats were received intratracheal instillation of normal saline（saline group, pH 5.3, 1.2 ml · kg^-1） or hydrochloric acid/NS （Hcl group and treatment groups, pH 1.2,1.2 ml · kg^-1）. Six hours later, the arterial gas was examined, the contents of TNF-α and IL-10 in the blood were assayed respectively, the extent of lung injury was further assessed by measuring the ratio of wet to dry weight and evaluating histological change of tissue slice under a light microscope. Results： （1） The most severe pathologic changes were detected in Hcl group, the extent of lung injury of Ambroxol treatment groups were less severe, but more severe than saline group. Among treatment groups, the pathologic changes of Hcl with low-dose of Ambroxol treatment group was the most serious, the extent of lung injury of Hcl with middle-dose of Ambroxol treatment group was less serious, but more serious than that of Hcl with high-dose of Ambroxol treatment group. （2）Compared with saline group, the W/D ratio and TNF-α, IL- 10 content in blood of Hcl group and treatment groups were obviously higher （ all P 〈 0. 05 ）, while the PaO2 was reduced （ all P 〈 0. 05 ）. T