罗氟司特对脂多糖诱导的急性肺损伤大鼠的保护作用

Roflumilast alleviates lipopolysaccharide-induced acute lung injury in rats

目的探讨磷酸二酯酶4抑制剂罗氟司特对脂多糖(LPS)诱导的急性肺损伤大鼠的保护作用。方法 30只健康雌性SD大鼠随机分为三组,每组10只。模型组和治疗组给予LPS 8 mg·kg^(-1)造模,对照组给予生理盐水。注入LPS前2 h,治疗组予罗氟司特5 mg·kg^(-1)灌胃。检测三组大鼠支气管肺泡灌洗液(BALF)中的细胞总数和中性粒细胞数,肺组织湿干重比及病理学评分。RT-PCR和Western blot测定肺组织上皮钠通道α(α-ENaC)的表达水平。结果与对照组相比,模型组BALF中细胞总数和中性粒细胞数、肺组织湿干重比和病理学评分增高(P<0.05或P<0.01),α-ENaC的蛋白和mRNA表达下降(P<0.05)。治疗组BALF中细胞总数和中性粒细胞数、肺组织湿干重比和病理学评分低于模型组,α-ENaC的蛋白和mRNA表达水平高于模型组,差异均有显著意义(P<0.05)。结论罗氟司特可通过促进肺组织α-ENaC的表达,减轻急性肺损伤大鼠的肺水肿,并可抑制炎症反应,对急性肺损伤大鼠有一定的保护作用。

AIM To investigate the effects of roflumllast on llpopmysaccnarlue （LPS）-induced acutelung injury （ALI） in rats. METHODS Thirty SD rats were randomly divided into 3 groups （n =10）, including control group, model group and trim group. In the model group and trial group, LPS was injected through left jugular veins with 8 mg .kg^-1 to build ALI model. Two hours before LPS injected, roflumilast was administrated intragastrically at 5 mg.kg^-1 in the trial group. Then the numbers of total cells and neutrophils in bronchoalveolar lavage fluid （BALF） were counted. Wet to dry ratio （W/D） of lung was analyzed. HE staining was used to observe lung injury score. RT-PCR and Western blot were included to measure the expression of α- epithelial sodium channel （α-ENaC）. RESULTS The numbers of total cells and neutrophils in BALF, W/Dand lung injury score were increased in the model group compared with the control group （P 〈 0.05 or P 〈 0.01）. And the expressions of eL-ENaC were reduced at both mRNA and protein levels in the model group （P 〈 0.05）. Compared with the model group, the numbers of total cells and neutrophils in BALF, W/D and lung injury score were reduced in the trial group and the expressions of cx- ENaC were up- regulated （P 〈 0.05） . CONCLUSION Roflumilast can alleviate LPS- induced lung edema via up- regulation α- ENaC and reducing inflammation response, indicating a protective effect of roflumilast in LPS induced ALI model in rats.