Establishment and analysis of cecal ligation puncture and lipopolysaccharide induced acute respiratory distress syndrome in rats

Abstract

Objective To investigate the possibility of cecal ligation puncture (CLP) combined with lipopolysaccharide (LPS) to establish acute respiratory distress syndrome (ARDS) model in rats, and to explore its significance and theoretical basis. Methods 176 SD rats were randomly divided into four groups, 44 rats in each group: (1)CLP group; (2)injection of LPS (2 mg/kg) through tail vein (LPS group); (3)CLP combined with injection of LPS (2 mg/kg) through tail vein (CLP+ LPS group); (4)injection of physiological saline (2 ml/kg) through tail vein after sham operation (control group). Each group was divided into four subgroups.The respiratory rate of rats, total number of white blood cells, percentage of polymorphonuclear leukocytes, total protein content, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid, and ratio of lung wet to dry weight were measured at 4th, 12th, 24th, and 48th hour.Observation of histopathological and transmission electron microscope on lung tissue was performed. Results Compared with the control group, the respiratory rate, total protein content, TNF-α, white blood cells, percentage of polymorphonuclear leukocytes, and IL-6 level increased at 4th hour in LPS group and CLP+ LPS group (all P<0.05), and increased at 12th hour in CLP group (all P<0.05). The above parameters in CLP group and CLP+ LPS group increased significantly at 24th hour (all P<0.05), while those tended to recover in LPS group.Respiratory frequency and IL-6 level were increased in CLP+ LPS group at all time points (all P<0.05). The results of pathological morphology and transmission electron microscopy showed that the inflammatory response and alveolar cell damage were the most severe in CLP+ LPS group at 24th hour. Conclusions Compared with the CLP or LPS models, lung injury is earlier and duration is longer in the rat models established by CLP combined with LPS.It is closer to the diagnostic criteria of ARDS on clinical manifestations and lung injury, and it is an ideal ARDS model. Key words: Cecal ligation puncture; Lipopolysaccharides; Respiratory distress syndrome, adult