Effect of alpha-melanocyte stimulating hormone on the apoptosis of the vascular endothelial cell of the lung in two-hit acute respiratory distress syndrome in rat]

OBJECTIVE: To investigate the effect of alpha-melanocyte stimulating hormone (alpha-MSH) on the apoptosis of the vascular endothelial cells of the lung in acute respiratory distress syndrome (ARDS) reproduced with acute hemorrhagic shock followed by intratracheal lipopolysaccharide (LPS, two-hit model) in rat. METHODS: Ten male Sprague Dawley rats, weighing (33.7+/-2.5) g, were randomly divided into two groups (A and B) with 5 in each group. All rats were anesthesized and ventilated mechanically with fractional concentration of inspired oxygen(FiO(2)) of 0.5, breath rate 100 times/min, tidal volume(V(T)) 12 ml/kg and inspiratory/expiratory ratio (I/E) 1:15. The blood was withdrawn to induce hemorrhagic shock via the carotid artery until blood pressure reached (45+/-5) mm Hg (1 mm Hg=0.133 kPa), which was maintained for 1 hour, and the shed blood and Ringer's lactate in volume equal to the shed blood were reinfused in 2 hours for resuscitation. Afterwards, LPS was given via the tracheal (200 microg/kg, in 500 microl normal saline) to establish the ARDS model. Group A was ARDS control group, group B was alpha-MSH administration group. alpha-MSH was intravenously administrated simultaneously, 3 hours and 6 hours after LPS given, the dosage was 17 mg/kg at each time point. The rats were sacrificed at 9 hours after LPS challenge, and the lung tissue was examined with microscope and electron microscope to observe the pathological changes and apoptosis of the vascular endothelial cells. RESULTS: In ARDS control group, remarkable infiltration of inflammatory cells was found in the alveoli, and the apoptosis of the vascular endothelial cells had developed to late stage. In alpha-MSH treatment group, few inflammatory cells were found in the alveoli, and the apoptosis of the endothelial cells was still in an early stage. CONCLUSION: alpha-MSH could inhibit the apoptosis of the vascular endothelial cells of the lung in the two-hit ARDS in rats. Therefore, it might have a protective effect on the lung after hemorrhagic shock and endotoxin challenge.