Objective: To investigate the anti-inflammatory effect of penehyclidine hydrochloride on oleic acid-induced acute respiratory distress syndrome (ARDS) in rats.
Methods: According to randomize number table method, 30 adult male Sprague-Dawley (SD) rats were divided into control group, model group and treatment group. Catheters were placed in femoral vein in each group. The control group was injected with 1.1 mL/kg physiological saline; the model group was injected with 0.1 mL/kg oleic acid and then injected with 1.0 mL/kg normal saline to establish ARDS model; the treatment group was injected with 0.1 mL/kg oleic acid and then injected with 1.0 mL/kg penehyclidine hydrochloride. At 3 hours after the model was established, blood gas analysis was carried out in each group, oxygenation index (PaO2/FiO2) was calculated, and the levels of serum interleukins (IL-1, IL-6) were measured by enzyme linked immunosorbent assay (ELISA). Rats were sacrificed to harvest lung tissue, and the lung wet/dry ratio (W/D) was calculated; the morphological changes of lung tissue was observed under microscope; the superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were detected by colorimetry; the expression of tumor necrosis factor -α (TNF-α) in lung tissue was detected by immunohistochemical method. The correlations between lung W/D ratio and various indicators were analyzed using Pearson correlation test.
Results: Compared with the control group, PaO2/FiO2 in model group was significantly decreased, lung W/D ratio was significantly increased, serum IL-1, IL-6 levels and lung tissue MDA content were significantly increased, lung tissue SOD activity was significantly decreased; the alveolar space was filled with exudate, neutrophils and red blood cells, and there were obvious edema and broadening in pulmonary interstitial and alveolar under light microscope; the type II alveolar epithelial cells were partly destroyed, accompanied by lamellar body degeneration and emptying phenomenon under electron microscope; and immunohistochemistry showed that the positive expression of TNF-α in lung tissue was significantly increased. Compared with the model group, PaO2/FiO2 in the treatment group was significantly improved [mmHg (1 mmHg = 0.133 kPa): 204.42±31.61 vs. 113.91±47.78, P < 0.05], the lung W/D ratio was significantly decreased (5.80±0.44 vs. 6.82±0.59, P < 0.01), serum IL-1, IL-6 levels and lung tissue MDA content were significantly decreased [IL-1 (μg/L): 18.38±0.28 vs. 20.04±0.39, IL-6 (μg/L): 12.64±0.67 vs. 14.28±1.33, MDA (nmol/mg): 3.95±0.28 vs. 5.17±0.29, all P < 0.05], the activity of SOD in lung tissue was significantly increased (U/mg: 48.75±2.41 vs. 45.09±1.69, P < 0.01), histological and pathological changes were significantly reduced, and the positive expression of TNF-α in lung tissue was significantly reduced [positive cell rate: (25.80±3.44)% vs. (38.82±3.59)%, P < 0.01].
Conclusions: Penehyclidine hydrochloride can effectively improve the oxygenation, alleviate lung injury and reduce pulmonary edema in oleic acid induced ARDS rat by decreasing lung W/D ratio, inhibiting oxidative stress and inflammatory response.