Abstract:

BACKGROUND: Obstructive sleep apnea hypopnea syndrome and chronic obstructive pulmonary disease are common diseases in respiratory system. The incidence of coexistence is high, which is called “overlap syndrome” in clinical practice. Chronic intermittent hypoxia is the basic pathological process of overlap syndrome.
OBJECTIVE: To investigate the mechanism of salidroside affecting the apoptosis and oxidative stress in lung injury caused by chronic intermittent hypoxia in mice.
METHODS: The study was approved by the Ethics Committee of Laboratory Animal Center of Southwest Medical University. Wild-type C57BL/6 male mice were randomly divided into normal control group, salidroside group, chronic intermittent hypoxia group and chronic intermittent hypoxia+salidroside group. The mice in the latter two groups were placed in an anoxic chamber. The complete cycle of hypoxia was adjusted to the initial oxygen concentration of 8% to 10% for 1 minute, and then rapidly converted to normoxia (19%-21%) for 2 minutes. The daily cycle of hypoxia was 8 hours for 30 days. On the day of hypoxia, mice in the salidrosidel and salidrosidel groups were given salidroside (50 mg/(kg·d) for 30 consecutive days. The pathological changes of lung tissue were observed under a light microscope. Quantitative and qualitative detection of oxygen free radical activity in mouse lung tissue was performed by chemical fluorescence method. The apoptosis related protein caspase-3, Bax, Bcl-2 levels, and Bax/Bcl-2 ratio were detected by western blot assay. 
RESULTS AND CONCLUSION: (1) The occurrence of chronic intermittent hypoxia activated the lung oxidative stress pathway and initiated cell apoptosis. The lung pathological damage in the chronic intermittent hypoxia group was more serious than that in the normal control group. Its pulmonary artery wall thickened in the normal control group, the alveolar size was uneven, the oxygen free radical activity was increased, the ratio of Bax/Bcl-2 and the protein level of caspase-3 were significantly increased (P < 0.05). However, the degree of lung pathological damage in the chronic intermittent hypoxia+salidroside group was significantly reduced and the above indicators in the chronic intermittent hypoxia+salidroside group were significantly lower than those in the chronic intermittent hypoxia group (P < 0.05). There was no significant difference in each indicator between normal control and salidroside groups (P > 0.05). (2) Therefore, salidroside may improve chronic intermittent hypoxic lung injury in mice by inhibiting oxidative stress response and apoptotic pathways.

Key words: salidroside, chronic intermittent hypoxia, lung, oxidative stress, apoptosis, oxygen free radical