[Protective effects of ulinastatin on phosgene-induced acute lung injury and relation to matrix metalloproteinase-9].
OBJECTIVE
To observe the protective mechanism of ulinastatin on mice with acute lung injury induced by exposure to phosgene and its relationship to the expressions of matrix metalloproteinase-9 (MMP-9) in the lung tissues.


METHODS
Sixty-four healthy male SD rats were randomly divided into two groups: the experimental group and the control group. 32 rats in the experiment group were randomly subdivided into four groups: rats with phosgene exposure group, rats with phosgene exposure after saline injected group, rats with phosgene exposure after dexamethasone injected group. 32 rats in the control group were randomly subdivided into four groups: rats with air exposure group, pretreated with ulinastatin before air exposure group, pretreated with saline before air exposure group, pretreated with dexamethasone before air exposure group, 8 animals in each group. After pretreated with the same dose of ulinastatin, saline, dexamethasone respectively, 32 rats in the control groups were exposed to the air on the same condition respectively for 5 min. While after pretreated with the same dose of ulinastatin, saline, dexamethasone respectively, 32 rats in the experiment groups were exposed to the phosgene which the concentration was 8.33 mg/L and with 100% purity for 5 min. The lung wet/dry (W/D) weight ratio was calculated, and total protein content and BALF leukocyte count were detected. The immunohistochemistry was used to detect lung tissue protein expression MMP-9 while enzyme-linked immunosorbent method was employed to detect MMP-9 in serum levels and enzyme original gelatinases spectrum method to detect BALF MMP-9 enzyme original content.


RESULTS
Compared with A1, A2, A3, A4 group, the lung W/D, BALF of protein content and WBC count in B1 and B2 group rats were significantly increased, and the difference was statistically significant (P < 0.01). There was statistically significant difference in lung W/D, BALF of protein content and white blood cell count between B1,B2 group and the B3 and B4 rats (P < 0.01). Histological experimental results showed marked hyperemia of alveolar walls, thickening in the lungs, alveolar walls and stroma cells infiltrating and more visible alveolar structure damage in B1 and B2 rats while the alveolar structure, the alveolar walls were clear and slightly thickened with inflammatory cells in B3 and B4 rats. Immunohistochemical result showed that the individual rats, lung and bronchus organization MMP-9 protein were weakly positive, B1 and B2 group MMP-9 protein expression was strongly positive,B3 group and the group MMP B4 lung tissue protein expression-9 weakens, restored to the normal lung tissue of weakly positive expression level. ELISA and gelatinases spectrum testing showed B1 and B2 rats, serum MMP-9 enzyme activity and content increased compared with A1, A2, A3, A4 group, the differences were statistically significant (P < 0.01), and B1, B2 group compared with the B3 and serum B4 group MMP-9 enzyme activity and the differences were obviously decreased, with statistically significant difference (P < 0.01).


CONCLUSIONS
Ulinastatin has protective effect on phosgene-induced ALL Ulinastatin can inhibit the up-regulation of expression of MMP-9.
Jinshan Hospital, Fudan University Chemical Injury Treatment, Shanghai 200540, China.
Wen-bin
WB
Huang
Jie
J
Shen
Lin
L
Zhang
Dai-kun
DK
He
Tie
T
Xu
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D006023:Glycoproteins / Q000627:therapeutic use*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010705:Phosgene / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006023:Glycoproteins; D010705:Phosgene; D020780:Matrix Metalloproteinase 9; C028665:urinastatin