Study on the therapeutic effect and related mechanism of ulinastatin on sepsis-related acute lung injury / 中国医师进修杂志

ABSTRACT

Objective:To explore the protective effect of ulinastatin on sepsis-related acute lung injury (ALI) in mice and its related mechanism analysis.Methods:A total of 50 male mice aged 6-8 weeks were selected and randomly divided into 5 groups, with 10 mice in each group. Group A was the sham operation group, group B was the sham operation and ulinastatin (30 000 U/kg) intervention group, group C was the simple cecal ligation and perforation (CLP) group, group D was the CLP+low-dose ulinastatin (15 000 U/kg) treatment group, and group E was the CLP+high-dose ulinastatin (30 000 U/kg) treatment group. Ulinastatin in groups B, D and E was injected intraperitoneally at the corresponding dose 1 h before CLP operation. The hematological characteristics, lung edema and inflammatory changes of lung tissue in mice of each group were evaluated and the expression levels of interleukin(IL)-6, tumor necrosis factor(TNF)-ɑ, IL-1β and nuclear factor(NF)-κB p65 mRNA and protein expression in blood and lung tissue were compared among the five groups.Results:Compared with that in group A, the lung water content in group C was significantly increased (78.68 ± 1.85)% vs. (51.98 ± 0.77)%, P<0.01. Compared with that in group C, pulmonary edema of the mice treated with ulinastatin was significantly reduced, with a certain dose-effect relationship. The wet weight/dry weight ratio of the lung tissue in group C was significantly higher than that of group A, B, D, E 4.74 ± 0.28 vs. 2.23 ± 0.16, 2.25 ± 0.22, 2.89 ± 0.31, 2.09 ± 0.12, P<0.01, and group E had the lowest ratio. After ulinastatin intervention, the inflammatory manifestations of the lungs were reversed in a dose-dependent manner. The degree of structural destruction was improved, and edema and polymorphonuclear neutrophil infiltration were reduced. Ulinastatin could significantly reduce the neutrophil and lymphocyte counts of mice after CLP treatment, reduce the expression of IL-6, TNF-α, IL-1β inflammatory cytokines and MPO activity. The reverse transcription-polymerase chain reaction (RT-PCR) results and Western blot analysis showed that the mRNA and protein expressions of NF-κB p65 in group C of lung tissue was significantly increased. However, after treatment with ulinastatin, it was significantly reduced, and it had a certain dose-effect relationship. Conclusions:Ulinastatin pretreatment can significantly reduce the expression levels of IL-6, IL-1β and TNF-α in sepsis-related acute lung injury, and can alleviate the inflammatory response in the lung. The protective effect of ulinastatin may be related to the inhibition of NF-κB pathway activation.