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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 |
Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016,China |
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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 lungtissue 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.
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Corresponding Authors:
Zhang Dan, E - mail: doctor_zhangdan@ 126. com
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