Inhibitory effects of protease inhibitor on endotoxin-induced acute lung injury in rats / 北京大学学报(医学版)

ABSTRACT

Objective:To investigate the efffects 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 O55B5, 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) ?g)] compared with group C[(4.95?0.08),(12.99?2.83) ?g], in the intervention groups((U5.0?)0.05,19.47?2.09;V4.98?0.06,21.44?3.12)however the difference was not significant between the intervention groups; The plasma endothelin-1 and lung tissue myeloperoxi- △Corresponding author’s e-mail, chenxuyan@medmail.com.cn dase 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 [UMDA((51.26)?5.56) nmol/g,C-diene(7.59?0.84) nmol/g;VMDA(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. Conclusion: 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.