Protection of Pirfenidone against an Early Phase of Oleic Acid-Induced Acute Lung Injury in Rats

摘要

The potential role of PFD [5-methyl-L-phenyl-2-(1H)-pyridone],an antifibrotic compound with anti-inflammatory effects,in several models of acute lung injury (ALI) has gained increasing attention;however,the protective effect of PFD in oleic acid (OA)-induced ALI remains unknown.We hypothesized that PFD protects from OA-induced ALI in rats,and we hoped to obtain the optimum preclinical conditions with PFD in ALI.Sprague-Dawley rats were randomized into five groups (five rats per group):normal control group,OA-treated group (0.15 ml/kg),and three PFD-treated groups (20,40,and 80 mg/kg p.o.,.,respectively).Arterial blood gases,lung wet/dry weight ratio,and postmortem histological changes were determined 0.5,1,2,6,and 24 h after OA challenge.Electron spin resonance spectroscopy was used for free radical detection and measurement.Experiments were examined based on the orthogonal test L4 (4~2) setting two factors (PFD dose and PFD valid time) with four different levels.The results of the orthogonal test showed that the sequence of effect of PFD was 0.5 h (oxygen radicals),1 h (histological changes),2 h (lung edema),and 6 h (partial pressure of oxygen) after OA challenge,and 40 mg/kg PFD was the most effective dose in this study.We conclude that PFD protects against OA-induced ALI in rats.The mechanism of these protective effects partly involves decrease of oxygen radicals.The data of this study proves that the orthogonal test will be a powerful method to help obtain the optimum experimental conditions with PFD in ALI in the future.