脂氧素A_4对急性肺损伤肺泡上皮通透性及claudin-4蛋白的影响

Effect of Lipoxin A_4 on Alveolar Epithelial Permeability and Protein Expression of Claudin-4 in Acute Lung Injury Induced by Lipopolysaccharide

目的探讨脂氧素A_4(lipoxin A_4,LXA4)对内毒素性急性肺损伤(acute lung injury,ALI)肺泡上皮通透性及claudin-4蛋白的影响。方法通过尾静脉注射脂多糖(lipopolysaccharide,LPS)制作大鼠内毒素性急性肺损伤模型,并予以脂氧素A_4治疗。测定各组大鼠肺泡上皮的通透性,观察肺组织形态学变化,检测肺组织湿干重比(wet to dry weight ratio,W/D),以及测定claudin-4蛋白含量。结果与内毒素损伤组相比,脂氧素A_4组可显著降低肺泡上皮通透性,改善肺组织形态,降低W/D,上调claudin-4蛋白表示水平。结论脂氧素A_4可降低急性肺损伤大鼠肺泡上皮通透性,减轻肺水肿,其机制可能与其上调claudin-4蛋白表达水平有关。

Objective To investigate the effect of lipoxin A4 on alveolar epithelial permeability and protein expression of claudin-4 in lipopolysaccharide（LPS）-induced acute lung injury（ALI）. Methods Rats were injected LPS via tail vein to establish the model of ALI. Lipoxin A4 was given at 6 hour after LPS injection. Alveolar epithelial permeability was evaluated by measuring bronchoalveolar lavage fluid and serum concentrations of evens blue. Lung injury was observed histologically in hematoxylin and eosin（HE） stained tissue sections, and the lung tissue mass alteration was measured by wet to dry weight ratio（W/D）.Protein expression level of claudin-4 was determined by western blot analysis. Results After lipoxin A4 treatment, alveolar epithelial permeability, lung injury and W/D were significantly decreased compared with ALI rats. Protein expression level of claudin-4 decreased in ALI rats and could increase significantly after lipoxin A4 treatment. Conclusion Lipoxin A4 could decrease alveolar epithelial permeability and alveolar fluid in ALI rats. The mechanism might be due to up-regulate protein expression of claudin-4.