国际麻醉学与复苏杂志   2015, Issue (5): 7-7
    
大剂量盐酸氨溴索对脂多糖致小鼠急性肺损伤的影响
许丹, 袁世荧, 刘梅1()
1.武汉市协和医院
Effect of large dose of ambroxol on lipolysaccharide-induced acute lung injury in rats
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摘要:

目的 研究大剂量盐酸氨溴索(沐舒坦)对脂多糖(lipopolysaccharides, LPS)所致小鼠急性肺损伤(acute lung injury, ALI)的治疗作用。 方法 雄性BALB/C小鼠24只,采用随机数字表法随机分为3组(每组8只):生理盐水组(A组)、LPS组(B组)、LPS+沐舒坦处理组(C组)。B组和C组予以LPS(2 g/L)3 mg/kg气管滴入制成ALI模型,A组予以等体积生理盐水气管滴入作为对照。6 h后,C组按100 mg/kg经尾静脉注入沐舒坦,A组和B组予以等体积的生理盐水,24 h后重复给药。造模后48 h收集肺泡灌洗液,测定灌洗液中脂氧素A4、肿瘤坏死因子(tumor necrosis factor, TNF)?蛳α、白细胞介素(interleukin, IL)-10、蛋白含量,并行多形核细胞计数;测定各组的肺湿/干重比、肺组织中性粒细胞髓过氧化物酶(myeloperoxidase of leukocytes, MPO)含量;苏木精-伊红(hematoxylin-eosin, HE)染色观察小鼠肺组织病理形态学变化。 结果 造模48 h后C组肺泡灌洗液中脂氧素A4[(332±19) ng/L]、IL-10含量[(36±6) ng/L]高于B组[(273±25)、(9±3) ng/L](P<0.01);C组TNF-α[(243±65) ng/L]、蛋白含量[(0.328±0.037) mol/L]、多形核细胞计数[(39.99±14.41)×104/ml]低于B组[(391±105) ng/L、(0.444±0.283) mol/L、(137.94±28.98)×104/ml](P<0.01);C组肺组织湿/干重比(3.65±0.18)及MPO含量[(6.4±0.4) U/g]低于B组[(4.37±0.58)、(137.9±29.0) U/g)](P<0.01);C组肺组织病理改变较B组明显减轻。 结论 100 mg/kg沐舒坦对LPS所致小鼠ALI有一定治疗作用,这一作用可能与促进炎症消退有关。

关键词: 脂多糖; 急性肺损伤; 盐酸氨溴索; 脂氧素A4
Abstract:

Objective To investigate the effect of high dose of ambroxol on lipolysaccharide(LPS)-induced acute lung injury(ALI) in rats. Methods Twenty-four male BALB/C rats were randomly divided into 3 groups(n=8): group A served as control group and received normal saline intracheally. Group B and group C received intracheal instillation of LPS(3 ml/kg). At 6 h after LPS or saline instillation, ambroxol(100 mg/kg) were administered into the tail vein in group C, and normal saline were administered at the same volume in group A and group B. Another dose of amborxol or normal saline were administered 24 h later. At 48 h after LPS or saline instillation, lipoxin A4, tumor necrosis factor(TNF)-α, interleukin(IL)-10, total protein and polymorphonuclear cells count in bronchoalveolar lavage fluid, and wet/dry weight ratio and myeloperoxidase(MPO) in lung tissues were measured. The morphopathogical changes in lung of mice were observed by hematoxylin?蛳eosin(HE) staining. Results At 48 h after LPS or saline instillation, lipoxin A4[(332±19) ng/L] and IL-10[(36±6) ng/L] in bronchoalveolar lavage fluid in group C were higher than that of group B[(273±25),(9±3) ng/L]. Levels of TNF-α[(243±65) ng/L], total protein[(0.328±0.037) mol/L], and polymorphonuclear cells count[(39.99±14.41)×104/ml] in group C were lower than that of group B[(391±105) ng/L,(0.444±0.283) mol/L,(137.94±28.98)×104/ml]. Wet/dry weight ratio(3.65±0.18) and MPO[(6.4±0.4) U/g] in lung tissues in group C were lower than that of group B[(4.37±0.58),(137.9±29.0) U/g)]. Morphopathogical changes of lung tissues were attenuated significantly in group C more significantly than that of group B. Conclusions Large dose of ambroxol might have the therapeutic efficiacy on LPS-induced ALI in rats partly through promoting the resolution of inflammation.

Key words: Lipolysaccharide; Acute lung injury; Ambroxol; Lipoxin A4