[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 The blood was withdrawn to induce hemorrhagic shock via the carotid artery until blood pressure reached (45+/-5) mm Hg (1 mm Hg=0.133 kPa), which was maintained for 1 hour, and the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.


CONCLUSIONS
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.
Department of Anaesthesiology, Changhai Hospita, Second Military Medical University, Shanghai 200433, China.
Yu-Liang
YL
Miao
Xiao-Ming
XM
Deng
Jin-Bao
JB
Li
Xiang-Kun
XK
Zhao
Jin-Mei
JM
Cao
Ye-Ping
YP
Tian
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000473:pathology*; D012771:Shock, Hemorrhagic / Q000150:complications / Q000473:pathology; D000521:alpha-MSH / Q000494:pharmacology*
D008070:Lipopolysaccharides; D000521:alpha-MSH