沐舒坦预处理对大鼠急性肺损伤的肺保护作用研究-东南大学学报医学版

沐舒坦预处理对大鼠急性肺损伤的肺保护作用研究

单位：东南大学附属中大医院胸外科, 江苏南京 210009

分类号：R-33;R965

出版年·卷·期（页码）：2014·33·第四期（468-473）

摘要：

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（10 mg·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（20 mg·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（40 mg·kg^-1·d^-1）]。稀盐酸吸入+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3 d。在第3天尾静脉注射沐舒坦或生理盐水30 min后，生理盐水组以1.2 ml·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1.2 ml·kg^-1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6 h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、PaCO₂、血清中TNF-α明显下降（均P<0.05），PaO₂、血清中IL-10水平明显增高（均P<0.05）；（4）稀盐酸吸入+沐舒坦低、中、高剂量处理组之间比较：随着沐舒坦剂量的递增，肺W/D 值、血清中TNF-α含量逐渐降低，PaO₂、血清中IL-10逐渐增高；沐舒坦低剂量组与沐舒坦中剂量组、沐舒坦低剂量组与沐舒坦高剂量组之间差异有统计学意义（P<0.05）；沐舒坦中、高剂量两组之间无显著差异（P>0.05），沐舒坦低、中、高剂量组之间PaCO₂差异无统计学意义（P>0.05）。结论：静脉应用大剂量沐舒坦预处理能有效减轻大鼠急性肺损伤的程度，且在一定剂量范围内，沐舒坦肺保护作用与其剂量呈正相关。

Objective: To investigate the protective effect of different dose of Ambroxol against Hcl-induced acute lung 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). The PaCO₂ of Hcl group was obviously higher than that of saline group(P<0.05), while there was no difference between saline group and treatment groups(P>0.05). (3)Compared with Hcl group, the W/D ratio, PaCO₂ and TNF-α in blood of treatment groups were reduced (all P<0.05), while the PaO₂ and IL-10 content in blood were higher (all P<0.05). (4)Comparison among treatment groups, the W/D ratio and TNF-α in blood were lower with the increasing dosage of Ambroxol, while the PaO₂ and IL-10 content in blood were higher. There was a significant difference between Hcl with low-dose of Ambroxol treatment group and Hcl with middle-dose of Ambroxol treatment group, as well as Hcl with low-dose of Ambroxol treatment group and Hcl with high-dose of Ambroxol treatment group (P< 0.05), but the difference between Hcl with middle-dose of Ambroxol treatment group and Hcl with high-dose of Ambroxol treatment group was not significant (P>0.05). The PaCO₂ was higher with the increasing dosage of Ambroxol, while there was no significant difference among treatment groups(P>0.05).Conclusion: Ambroxol can obviously reduce the extent of acute lung injury induced by Hcl, and within a certain range of dosage, the lung protective effect and dosage of Ambroxol are positively correlated.

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