Effects and mechanisms of oridonin in the treatment of acute respiratory distress syndrome mice

Objective: To investigate the protective effects and possible mechanisms of oridonin (ORI) in the treatment of acute respiratory distress syndrome (ARDS) in mice. Methods: ARDS mice models were established by tracheal instillation of lipopolysaccharide (LPS). Male C57BL/6 mice aged from 8 to 10 weeks were randomized into three groups: a sham operation group (5 mice), in which only sterile phosphate buffered saline (PBS) was instilled into the trachea; an experimental group, in which after the establishment of ARDS mice models, different doses of ORI (30 mg/kg, 90 mg/kg, 150 mg/kg, 300 mg/kg respectively; 5 mice in each group) were given by intraperitoneal injection; and a control group, in which the same doses of PBS were given (5 mice). The lung injuries were observed on the base of the detection of protein quantification in alveolar lavage fluid, the lung wet-to-dry ratio (W/D), and the pathological sections of lung tissues stained with hematoxylin and eosin (HE). The expression of inflammatory factors in lung tissues of the mice in these two groups was detected by fluorescent quantification polymerase chain reaction (PCR) and the release of inflammatory factors was detected by enzyme-linked immuno sorbent assay (ELISA); western blot was employed to analyze the activation of the NF-κB’s pathway. Results: Compared with the control group, protein quantification in bronchoalveolar lavage fluid and the lung W/D ratio were significantly reduced after the injection of ORI (P<0.05). The pathological sections showed that the inflammation in lung tissues was relieved and the injuries were significantly reduced. The expression of TNF-α, IL-6 in lung tissues and serum greatly decreased (P<0.05). The results of western blot showed that the expression of NF-κB p65 in the experimental group decreased and the expression of Iκ-Bα increased. Conclusion: ORI could alleviate ARDS lung injuries by inhibiting the activation of signaling pathway of NF-κB and the expression of inflammatory factors.