西地那非对脂多糖诱导的小鼠急性肺损伤的作用

目的明确西地那非对急性肺损伤(ALI)的治疗作用及可能机制。方法采用脂多糖(LPS,4 mg·kg~(-1))气道滴入诱导的小鼠ALI模型。随机分为生理盐水组、LPS模型组、西地那非3,10及30 mg·kg~(-1)组、地塞米松5 mg·kg~(-1)组。测定肺干/湿重比值,常规细胞形态学检测支气管肺泡灌洗液(BALF)中白细胞,肺组织切片观察病理改变;测定肺组织匀浆髓过氧化酶(MPO)活性、NO含量、NOS活性及TNF-α含量。结果LPS诱导的ALI小鼠肺干/湿重比值明显下降;BALF中白细胞总数及中性粒细胞比例明显增加;肺毛细血管通透性明显增加;肺组织间隙大量中性粒细胞浸润和红细胞渗出;肺组织匀浆TNF-α含量和MPO活性明显增加,NO含量、总NOS活性及iNOS活性明显增加。同时腹腔注射西地那非可剂量依赖性地降低ALI小鼠肺干/湿重比值;减少BALF中的白细胞总数及中性粒细胞的比例;降低肺毛细血管通透性;改善肺组织病理变化;抑制肺组织匀浆TNF-α含量、MPO活性及NO含量、总NOS活性及iNOS活性的增加。结论西地那非对LPS诱导的ALI有保护作用,提示NO- cGMP途径可能在ALI中起重要作用。

Effect of sildenafil on lipopolysaccharide-induced acute lung injury in mice

AIM To investigate the effect of sildenafil on acute lung injury (ALI) and its anti-inflammation mechanism. METHODS ALI was induced in male ICR mice by intratracheal administration of lipopolysaccharide (LPS, 4 mg·kg^-1). All mice were randomly divided into six groups: control group, LPS group, dexamethasone 5 mg·kg^-1, sildenafil 3, 10 and 30 mg·kg^-1. The effect of sildnafil on ALI was observed 6 h after LPS instilled. Lung dry weight/wet weight ratio and permeability were detected. Neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and lung tissues were determined by cell count and morphological analysis. The level of tumor necrosis factor (TNF)-α was detected with ELISA. Myeloperoxidase(MPO) activity，nitric oxide (NO) and nitric oxide synthase (NOS) were measured according to the specification. RESULTS LPS induced a decrease in lung dry weight/wet weight ratio, and significantly increased in total leucocyte number and neutrophil percent in the BALF at 6 h after intratracheal administration with LPS. Neutrophil infiltration and lung edema in the lung tissue, the level of MPO, NO and NOS activity markedly increased. TNF-α level was sharply increased. Sildenafil (3, 10 and 30 mg·kg^-1, ip) decreased the total leucocyte number and neutrophil in the BALF, MPO activity, NO content and NOS activity of lung tissue in dose-dependent manner. CONCLUSION Sildenafil has protective effect on ALI mice,suggesting that it be used in ALI.