Protective effect and mechanism of RSR13 on lung blast injury in rats at high altitude

Objective To investigate the impact and mechanism of efaproxiral (RSR13), a hemoglobin allosteric agent, on lung injury in rats caused by explosion-induced shock waves in plateau areas. Methods Eighty-two healthy male SD rats (8-week-old, transferred from an altitude of 2 880 m to 4 700 m within 6 h) were randomly divided into blast injury group and RSR13+blast injury group (intraperitoneal injection of 150 mg/kg RSR13 2 h before explosion). Sixty rats were positioned at 5 m from the explosion source and divided into 5-m blast injury group (n=30) and 5-m RSR13+blast injury group (n=30). Additionally, 16 rats were positioned at 6 m from the explosion source and then assigned into 6-m blast injury group (n=8) and 6-m RSR13+blast injury group (n=8). The left 6 rats served as control (n=6). Survival outcomes of each rat group positioned 5 m from the explosion source were observed over a 24-hour period. HE staining was used to evaluate the pathological score of the surviving rats positioned at 6 m from the explosion source in 24 h after explosion, along with arterial blood gas analysis. The contents of glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) in the lung tissues were determined by colorimetry. Western blotting was conducted to measure the expression levels of cleaved caspase-3 and occludin in the lung tissue. Results RSR13 pretreatment increased the survival rate immediately after explosion (93.3% vs 46.7%, P < 0.01) and at 1 h after explosion (86.7% vs 46.7%, P < 0.01) in plateau areas of 5 m from the explosion source. At high altitude, RSR13 pretreatment reduced the pathological score of lung injury in rats 6 m away from the explosion source (8.27±0.93 vs 13.70±0.78, P < 0.01), but had no significant effect on the results of arterial blood gas analysis in rats with lung blast injury (P>0.05). In addition, RSR13 pretreatment also increased GSH content (40.27±12.47 vs 22.62±10.88 μg/g, P < 0.05), but showed no obvious effect on MDA content and SOD activity (P>0.05), decreased the protein level of cleaved caspase-3 (P < 0.01) and increased that of occludin (P < 0.05) in the lung tissues. Conclusion RSR13 exerts significant protective effect on lung injury in rats caused by explosion-induced shock waves in high-altitude environment, which may be related to its increasing antioxidant capacity, reducing cell apoptosis and decreasing barrier permeability of lung ventilation.