ABSTRACT
Hyperoxic acute lung injury (HALI) is caused by prolonged exposure to high oxygen partial pressure. This study was undertaken to investigate the protective effects of oridonin on HALI in a mouse model. Mice were randomly divided into three groups: the control group, HALI group and oridonin (ORI) group. HALI was induced by exposing mice to pure oxygen at 2.5 atmospheres absolute (ATA) for six hours in the HALI and ORI groups. In the ORI group, mice were intraperitoneally injected with ORI at 10 mg/kg twice daily after hyperoxic exposure. Animals were sacrificed 24 hours after the hyperoxia exposure, followed by bronchoalveolar lavage fluid (BALF). Lungs were then collected. Each lung was processed for HE staining and detection of wet-to-dry weight ratio. The lactate dehydrogenase (LDH) activity and protein content of BALF were determined, and the contents of malonaldehyde (MDA), glutathione (GSH), tumor necrosis factor alpha (TNF-?) and interleukin-10 (IL-10) in the lung were measured. Our results showed prolonged exposure to hyperoxia significantly damaged the lung, caused lung edema, increased MDA and TNF-?, and reduced GSH and IL-10 in the lung. However, post-exposure treatment with oridonin was able to improve lung pathology, attenuate lung edema, reduce MDA and TNF-?, and increase GSH and IL-10 in the lung. These findings suggest that oridonin can protect the lung against hyperoxia-induced injury in mice.
Subject(s)
Acute Lung Injury/drug therapy , Diterpenes, Kaurane/therapeutic use , Oxygen/adverse effects , Protective Agents/therapeutic use , Acute Lung Injury/etiology , Animals , Atmospheric Pressure , Bronchoalveolar Lavage Fluid/chemistry , Disease Models, Animal , Glutathione/analysis , Interleukin-10/analysis , L-Lactate Dehydrogenase/analysis , Lung/chemistry , Malondialdehyde/analysis , Mice , Partial Pressure , Pulmonary Edema/drug therapy , Pulmonary Edema/etiology , Random Allocation , Time Factors , Tumor Necrosis Factor-alphaABSTRACT
Current study findings concerning changes in the renin-angiotensin system (RAS) in cases of hyperoxic acute lung injury (HALI) have shown conflicting results. This study aimed to detect the angiotensin II (Ang II) and angiotensin-converting enzyme (ACE) in a rat HALI model. Healthy male Sprague-Dawley rats were randomly assigned into three groups: the control group, HALI group and hyperbaric oxygen preconditioning (HBO2-PC) group. HALI was induced by exposure to pure oxygen at 250 kPa for six hours. In the HBO2-PC group, rats were exposed to oxygen at 250 kPa for 60 minutes twice daily for two consecutive days; HALI was induced at 24 hours after the last oxygen exposure.=After HALI, the lung, spleen and liver were harvested for HE staining and pathological examination. At one hour and 18 hours after HALI, the blood, liver, lung and spleen were collected for the detection of Ang II and ACE contents by enzyme-linked immunosorbent assay. Pathological examination showed the lung was significantly damaged and characteristics of HALI were observed, but there were no significant pathological changes in the liver and spleen. After HALI, Ang II and ACE contents of different tissues increased progressively over time, but the HBO2-PC group showed reductions in the Ang II and ACE contents to a certain extent, especially at 18 hours after injury. These findings suggest prolonged hyperoxia exposure may activate the RAS, which may be associated with the pathogenesis of HALI. HBO2-PC has a limited capability to inhibit RAS activation.
