The effects of a graded increase in chronic hypoxia exposure duration on healthy rats at high-altitude

To investigate the effects of chronic hypoxia exposure at high altitude on the formation of pulmonary edema in rats, we randomized rats into normoxic control groups and hypoxic 24, 48, and 72-hour exposure groups. In the hypoxic exposure group, the arterial blood gas, wet-dry weight ratio (W/D), lung tissue permeability index (LPI), bronchoalveolar lavage fluid (BALF) and plasma levels of the inflammatory factors were measured after continuous, chronic hypoxic exposure for a corresponding time, and the pathological changes in the lung tissue and the expression of tight junction-associated protein occludin were observed. We found that the contents of arterial blood gas, W/D, LPI, BALF and plasma IL-6, TNF-α, and IL-10 in the hypoxic exposure group were significantly different from the contents of arterial blood gas in the normoxic control group. H&E staining showed tissue effusion, a marked thickening of the pulmonary septum, interstitial inflammatory cells, and erythrocytic infiltration. Compared with the normoxic control group, the pulmonary edema score was significantly increased in the hypoxic 48-hour group. Toluidine blue staining showed that the mast cell count and degranulation rate were significantly increased in the hypoxic 48-hour and 72-hour groups, but massone staining showed no significant pulmonary interstitial fibrosis in the 4 groups. Occludin expression was significantly higher in the normoxic control group than it was in the hypoxic exposure group. These results indicated that different chronic hypoxic exposure durations at the plateau all caused high-altitude pulmonary edema in rats, but there was no significant difference in some indicators among the groups.