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| Protective effect of ulinastatin on acute lung injury and its mechanism in mice |
| Li Xue-ning, Cao Chao, Shou Song-tao, Wang Jun, Chai Yan-fen |
| Emergency Medicine Department, Graduate College, Tianjin Medical University, Tianjin 300052, China |
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Abstract Objective To investigate the protective effects and the mechanisms of ulinastatin (UTI) on LPS-induced acute lung injury (ALI) in mice. Methods Total of 64 SPF male C57/BL mice were randomly divided into four groups: Sham, Sham+UTI, LPS, LPS+UTI, 16 mice in each group. The mouse model of ALI was established by instilled the lipopolysaccharide (5 mg/kg) into the trachea. In Sham+UTI group and LPS+UTI group, mice were treated with UTI (10 000 U/kg) hypodermic injected before model establishment 30 minutes. Sham group and LPS group were treated with the equivalent normal saline. 72 h survival rate of mice were observed. Another 64 mice were divided into the above mentioned method. The bronchoalveolar lavage fluid (BALF) and lung tissue were obtained at 24 h after LPS treatment. The total cell count, neutrophil count and macrophage count in the BALF were determined; the wet/dry (W/D) weight ratio of the lung tissue were measured; hispathological changes and pathology scores of the lung tissue were observed by HE staining; myeloperoxidase (MPO) activity and malondialdehyde (MDA) contents in the lung tissue homogenate were measured; mRNA level of tumor necrosis factor (TNF-α), interleukin-1 (IL-1), interleukin-6(IL-6), interleukin-2 (IL-2) in the lung tissue were measured by real-time PCR; the expression of TLR4/NF-κB p-65 were detected by RT-PCR and Western blot. Data analysis using SPSS 21.0 Software, multiple-group comparisons were performed using one-way ANOVA, the intergroup comparisons were analyzed by the LSD-t test with P<0.05 for the statistically significant difference. Results The survival rate, lung W/D ratio, hispathological changes, pathological scores, pulmonary MPO activities and MDA contents, mRNA levels of TNF-α, IL-1, IL-6, IL-2, TLR4/NF-κB mRNA were all lower in LPS+UTI group than those in LPS group, the difference was statistically significant (P<0.05 or P<0.01). Conclusion UTI can inhibit the inflammatory response of LPS-induced ALI in mice. This protective effects may be work by effecting TLR4/NF-κB signaling pathways.
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Corresponding Authors:
Chai Yan-fen, E-mail: Chaiyanfen2012@126.com
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