关键词: 急性肺损伤, 乌司他丁, miRNA21, PDCD4, TNF-α

Abstract: Objective: To investigate the effect of ulinastatin（UTI） in lipopolysaccharide（LPS） -induced acute lung injury (ALI) and its potential regulation on miRNA21 in mice. Methods: C57BL/6 mice(n=40) were randomly divided into control group, LPS group、UTI-L group and UTI-H group with 10 mice in each group using random number table. The pathological changes of lung tissue were evaluated by hematoxylin-eosin(HE) staining. The concentrations of total protein in bronchoalveolar lavage fluid(BALF) were assessed by bicinchoninic acid(BCA) method. In BALF, the activity of myeloperoxidase(MPO) was detected by an MPO assay kit and the levels of interleukin-1β(IL-1β)、tumor necrosis factor-α(TNF-α) were determined by enzyme linked immunosorbent assay(ELISA). The total cell counts and polymorphonuclear(PMN)counts in the BALF were analyzed by Giemsa staining. The levels of miRNA21 and mRAN levers of PDCD4 were assessed by qPCR, while the levels of PDCD4 were determined by Western blot. Results: Compared with control group, the classic ALI pathological changes were observed in the mice in LPS group ,manifesting by increases in W/D weight ratio ,total protein levels, cell counts、 IL-1β、TNF-α levels and MPO activities in the BALF, accompanied with up-regulated levels of miRNA21,down regulated levels of PDCD4 proteins in the lung tissues(P＜0.05).The deteriorating effects triggered by LPS were significantly reversed by administration of UTI. UTI displayed beneficial effects on LPS-induced ALI, as evidenced by alleviated lung injury, decreased levels of W/D weight ratio , protein levels, cell counts ,MPO activities and IL-1β、TNF-α levels in the BALF(P＜0.05),and decreased levels of miRNA21, increased levels of PDCD4 proteins in the lung tissues(P＜0.05).Meanwhile, LPS-induced enhanced levels of miRNA21 was dose-dependently inhibited by UTI. However, the levels of PDCD4 mRNA have no difference among the four groups. Conclusions: UTI protects against LPS-induced ALI in the mice by down-regulating miRNA21 and enhancing levels of PDCD4 proteins.

Key words: ARDS, ulinastatin, miRNA21, PDCD4, TNF-α