[Inhibitory effects of protease inhibitor on endotoxin-induced acute lung injury in rats].
OBJECTIVE
To investigate the effects of protease inhibitor on lipopolysaccharide-induced acute lung injury in rats and its possible mechanisms.


METHODS
Thirty-two male Wister rats, weighting 250-270 g, were divided into four groups randomly. C, normal controls (n=8); A: acute lung injury group (n=8), receiving intravenous endotoxin (lipopolysaccharide O55:B5, LPS 5 mg/kg); V, low-dose group (n=8), U, high-dose intervention group (n=8, receiving Ulinastatin 50,000 U/kg and 100,000 U/kg respectively and LPS 5 mg/kg). The specimens were collected 2 hours later, We observed the following changes: blood gas analysis, the lung wet/dry weight ratio, the pulmonary vascular permeability, histological manifestations, lung tissue myeloperoxidase activity, plasma endothelin-1, lung tissue malonaldehyde and conjugated-diene.


RESULTS
Compared with Group C, the lungs of the rats in Group A had significant hyperemia and spotted hemorrhage. The inflammatory granulocyte infiltrating, diffused alveolar septum thickening and spotted hemorrhage were observed in pathological examinations. The lung wet/dry weight ratio and Evans Blue content (per gram) increased significantly in group A [(5.41+/-0.06), (27.64+/-2.48) microg] compared with group C [(4.95+/-0.08), (12.99+/-2.83) microg], in the intervention groups (U: 5.0+/-0.05, 19.47+/- 2.09; V: 4.98+/-0.06, 21.44+/-3.12) however the difference was not significant between the intervention groups; The plasma endothelin-1 and lung tissue myeloperoxidase activity increased significantly in group A [(948.23+/-103.45) u/g, (152.90+/-8.41) u/g] compared with group C [(729.38+/-88.64) u/g ], [(54.62+/-15.49) u/g] but intervention groups [U: (633.27+/-93.27) u/g, (119.40+/-11.32) u/g; V: (671.87+/-105.45) u/g, (129.55+/-9.57) u/g] decreased significantly compared with group A, no significant difference between intervention groups; lung tissue Lipid-peroxide (malonaldehyde, MDA and conjugated-diene, C-diene) increased significantly in group A [MDA: (73.95+/-4.62) nmol/g; C-diene: (10.96+/-0.81) nmol/g] compared with group C [MDA: (39.65+/-6.21) nmol/g; C-diene: (3.34+/-0.51) nmol/g], intervention groups [U: MDA: (51.26+/-5.56) nmol/g, C-diene: (7.59+/-0.84) nmol/g; V: MDA: (59.87+/-4.62) nmol/g, C-diene: (8.79+/-0.45) nmol/g] decreased significantly compared with group A. MDA decreased significantly in group U compared with group V.


CONCLUSIONS
The protease inhibitor, Ulinastatin, may decrease inflammatory reaction and further decrease lung damage induced by LPS in rats, all indicating protection of protease inhibitor against acute lung injury.
Chen
Xu-yan
XY
Department of Emergency Medicine, Peking University First Hospital, Beijing 100034, China. chenxuyan@medmail.com.cn
Wang
Bo
B
Tan
Wei
W
Xiong
Hui
H
Li
Xiu-qing
XQ
Gao
Yu-song
YS
Tian
Ya-nan
YN
Liu
Xin-min
XM
D000818:Animals; D006023:Glycoproteins / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D011480:Protease Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D006023:Glycoproteins; D008070:Lipopolysaccharides; D011480:Protease Inhibitors; D008315:Malondialdehyde; D010544:Peroxidases; C028665:urinastatin