Effect of high volume mechanical ventilation on radiation-induced lung toxicity in rats

Objective To evaluate the effects of mechanical ventilation on radiation induced lung injuries of apoptosis, acute inflammation, and oxidative stress by establishing a rat mechanical ventilation model and animal model. Methods Totally 40 male Sprague-Dawley(SD) rats were randomly divided into 4 groups with 10 rats in each group: control, radiation alone, high tidal volume ventilation, and high tidal volume ventilation following by radiation. After treatment, the pathological changes in lung tissue were observed, NF-κB activity was detected by electrophoretic mobility shift assay (EMSA), the expression of NF-κB subunit P65 protein level in lung cell nucleus was detected by Western blot, and the apoptosis of lung cells was detected by terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) method. The wet to dry weight ratio (W/D) of lung, myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected. In addition, the total protein and white blood cell number in lung lavage fluid were also measured. Results Compared to the control, the acute lung injury (ALI) score, W/D ratio, MPO activity, total protein level, white blood cell number, apoptosis index (AI), lung tissue MDA, NF-κB activity and P65 protein expression were increased significantly (q =0.000 32-0.004 81, P<0.05), while SOD values was decreased significantly (q =0.000 18-0.002 53, P<0.01), in other three groups. Compared with radiation and high tidal volume ventilation group, the above indexes were significantly higher (q =0.004 3-0.022 6, P<0.05) but the SOD value was significantly lower (q =0.002 9-0.008 3, P<0.05) than those in the high tidal volume ventilation plus radiation group. Conclusions High tidal volume ventilation delivered to the radiation group produced more transparent ventilator-induced lung injury (VILI) than the high tidal volume ventilation alone induced VILI including permeable pulmonary edema, acute inflammation, oxidative stress and apoptosis in lung. Key words: Ventilator; Radiation-induced lung injury; Inflammatory response; Oxidative stress; Apoptosis