| Objective:Ulinastatin (UTI) was used for intervening the rats suffered from phosgene-induced acute lung injury, to investigate whether it is effective when ulinastatin was dosed after the rats exposed to phosgene, and whether there is a steady correlation between the benefit and doses of the drug, to study the role of interleukin-15(IL-15) and intercellular adhesion molecule-1(ICAM-1) in the disease, understanding the possible mechanism of phosgene-induce acute lung injury.Materials and Methods:Part1.-80male Spraque-Dawley (SD) rats were incruited in the experiment. The aninals were devided into8groups randomly, including the air control group (Group Ai), the phosgene inhaled group (Group Ph), the preventive ulinastatin group (Group Be), the ulinastatin400kU/kg group (Group Uh, therapeutic), the ulinastatin100kU/kg group (Group Um, therapeutic), the ulinastatin3.3kU/kg group (Group Ul, therapeutic), the0.9%NaCl group (Group Np) and the dexamethasone control group (Group Dx). They were exposed to phosgene for5min, except the animals in Group Ai. The concentration of the gas was5.0gram per cubic metre. The rats were sacrificed6hours after phosgene inhalation. The lung, BALF (Bronchoaleolar lavage fluid) and blood were collected. The pulmonary congestion area rates were measured, the lung wet weight/dry weight ratios (W/D) were calculated, cells in the BALF were counted and classified, and the lung tissue phathogenic slices were observed.Part2:Among the groups,the concentrations of ICAM-1and IL-15in serum of the rats were detected by ELISA. All statistical analyses were carried out using Stata7.0. Comparisons between groups were performed using Krusal-Wallis test.Results:Part1:Pulmonary edema and cytoexudation (p=0.0015) were observed after the rodents exposed to phosgene. The lung injury alleviated in all of the ulinastatin therapeutic dosing groups,and the cells exudated to pulmonary alveoli reduced (p=0.0039,0.0009and0.0171). The curative effect in Group Uh was better than Group Ul. The benefit of Group Um was more than Group Dx (p=0.0209) and Group Be (p=0.0384), from the aspect of total cells concentration in BALF. However, dexamethasone and normal saline did not significantly inhibit pulmonary edema,refering to the ratios of W/D.Part2:(1) The concentration of ICAM-1in serum in Group Ph was obviously higher than the one in Group Ai (p=0.0006). The concentration of ICAM-1in serum in Group Um was significantly lower than the one in Group Ph (p=0.0063). The change in Group Ul was similar with Group Um. Moreover, serum ICAM-1in Group Uh was significantly lower than that in Group Um (p=0.0192) and Group Ul (p=0.0099). It implies that the effect of high dose of ulinastatin is the best.The effect of ulinastatin decreasing concentration of serum ICAM-1was better obvious than that of dexamethasone. The benefit of therapeutic administration in reducing serum ICAM-1was as well as pre-treatment.(2) The concentration of IL-15in serum in Group Ph was markedly higher than the one in Group Ai (p=0.0009). The concentration of IL-15in serum in Group Um was obviously lower than that in Group Ph (p=0.0095). This result suggests that the expression or release of IL-15is inhibited by ulinastatin after the rats exposed to phosgene. Surprisingly, the concentration of IL-15in serum had no statistically significant difference btween Group Ul and Ph (p=0.2887). Concentration of serum IL-15had a negative correlation with doses of ulinastatin. The level of IL-15in Group Uh was markedly lower than Group Dx (p=0.0118). The level of IL-15was not signifidcantly changed by preventive ulinastatin (p=0.2895). The level of IL-15in Group Um was markedly lower than in Group Be (p=0.0205), suggests that the benefit of therapeutic administration in reducing serum IL-15was more than that of pre-treatment.Conclusion:This research finds that in early phase of phosgene-induced acute lung injury, the main exudated composition is red blood cell, but not many inflammatory cells. Derect damage is the dominant lung injury in early time of phosgene inhalation. In this stage, the secondly inflammatory injury has started. Effect of ulinastatin on inhibiting lung injury could be obtained by therapeutic dosing. The lungs of the rats in low dose group were also protected, but the effect in high dose group was better than that in low dose group. Rate of pulmonary congestion area, total cells concentration in BALF and erythrocytes concentration present a similar trend as ratio of W/D. Our data suggest that these changes may be useful indicators. IL-15may regulate the level of ICAM-1by chemical attracting neutrophils, to make neutrophils affix to vascular endothelial cells or the cells in the lung. The levels of IL-15and ICAM-1in serum are inhibited by ulinastatin after the animals exposed to phosgene. |
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