Abstract:

Objective To observe the alterations of macrophage M1 and M2 subsets and the regulation of Ulinastatin（UTI）and to explore the mechanisms of UTI anti-inflammatory in the immunocompromised mousewith severe pulmonary infection. Methods A total number of 60 Balb/c mice were randomly divided into control group，model group and UTI-group，with 20 mice in each group. The mice in model group were prepared withmethylprednisolone by intraperitoneal injectionand dripping LPS bytrachea. The mice inUTI-group were treated by intervention with UTI（1×105U/kg），before or after LPSIntervention. At6 hours after theintratracheal administration of LPS，the indexes were detected as fellow: the cell types and ratios of cells in bron choalveolar lavage fluid（BALF），pathological changes expression of CD163 in the lung of mice were detected by hematoxylin-eosin（HE）staining and immunohistochemistry staining，respectively. The mRNA expression of M1-type markers（TNF-α，IL-6，iNOS）andM2-type markers（CD206，Arg-1，IL-10）were analyzed by real-time quantitative PCR in BALF. Results There was acute respiratory distress phenomenon in the model group. The pathological changes were wider alveolar walls and predominant polymorphonuclear neutrophils（PMN）and mononuclear inflammatory infiltrates. In UTI group，the pulmonary injury were alleviated and lung injury score were significantly lower than that of model group〔lung injury score（score）：6.77±0.85 vs. 8.21±0.92，P ＜ 0.05〕. The ratios of PMN and macrophage were significantlyincreased in in UTI group and model group，but there were no significant difference between the two groups. Except iNOS，the markers of M1 and M2 macrophages were higher than those of control group. In UTI group，M1-type markers（TNF-α，IL-6）and M2-type markers（CD206，IL-10）were significantly lower than that in model group〔TNF（2-ΔΔCt）：0.42±0.18vs. 0.76±0.17，IL-6（2-ΔΔCt）：0.72±0.26 vs. 1.22±0.32，IL-10（2-ΔΔCt）：3.91±1.35vs. 6.84±2.13，CD206（2-ΔΔCt）：0.61±0.19 vs.0.92±0.31，allP ＜ 0.05〕，ad iNOSndArg-1hadnosignificant difference. In additional，M2-type marker CD163 expression in UTI group was significantly lower than that of model group，but higher than that of control group〔CD163（A）value ：31 430.0±2 417.97 vs. 69 855.0±6 489.5，P ＜ 0.05〕. Conclusion In the immune suppression mice of Th1 to Th2 of unidirectional deviation，M1 macrophage subset was activated more strongly than M2 macrophage subsets in severe pulmonary infection.The mechanisms of UTIanti-inflammatory may regulate of rebalance of M1 and M2 macrophages.