Ulinastatin improved the lung injury of the septic mice induced by lipopolysaccharide through the Rho/ROCK signaling pathway

WEI Fu; ZHANG Dan; ZENG Yan; XU Shan; LUO Li

doi:10.3969/j.issn.1002-1949.2016.01.008

Abstract：Objective To investigate the influence of Ulinastatin (UTI) on the lung injury of the septic mice induced by lipopolysaccharide (LPS) and clarify the molecular mechanism. Methods Septic mice model was induced by intravenous administration of LPS. The C57BL/ 6 mice were randomly divided into 3 groups: control group (Con group, n = 10), LPS model group (LPS group, n = 10) and UTI intervention group (L + U group, n = 30). Lung wet / dry weight (W/ D) ratio and Evans Blue (EB) were used to detect the water content and the capillarity permeability respectively; HE staining was used to observe the pulmonary histopathology; the expressions of VE - cadherin and ROCK2 were measured by immunohistochemical assay. Results Compared with control group, both the W/ D ratio and EB content of lung increased significantly in LPS group (all P < 0. 05), while in L + U group , the W/ D ratio and EB content of lung decreased obviously. When the mice were treated with UTI at the dose of 104 U/ kg and 105 U/ kg, a significant decrease in both the W/ D ratio and EB content of lung were observed compared with LPS group (all P < 0. 05). Compared with control group, the destruction of lung tissue in LPS group was serious, and this phenomena could be improved by UTI. Immunohistochemical results showed that a significant downregulation of VE - cadherin and a significant upregulation ROCK2 in LPS group compared with control group (all P < 0. 05), while the treatment with UTI could alleviate this phenomena (all P < 0. 05). Conclusion UTI could improve the lung injury in a dose - dependent manner by alleviating the vascular hyper - permeability in the septic mice model induced by LPS,while this effect may be related to the Rho/ ROCK signaling pathway.