中文摘要：

目的探讨乌司他丁（UTI）对脂多糖（LPS）诱导脓毒症小鼠肺损伤的保护作用及其分子机制。方法将C57BL／6小鼠随机分为对照组（Con组，n=10）、模型组（LPS组，n=10）及UTI干预组（L＋U组，n=30），建立LPS脓毒症小鼠模型。采用肺湿干质量（W／D）法及伊文思蓝（EvansBlue，EB）法观察各组小鼠肺组织含水量及肺微血管通透性的变化，HE染色法检测各组小鼠肺组织病理变化，免疫组化法检测肺组织血管钙黏蛋白（VE-cadherin）及ROCK2的表达。结果与Con组比较，LPS组小鼠肺组织W／D及EB含量均明显增加（均P〈0．05），而L＋U组W／D及EB含量明显降低，其中UTI在10^4U／kg、10^5U／kg剂量时，与LPS组比较差异有统计学意义（均P〈0．05）；LPS组小鼠较Con组肺组织损伤严重，L＋U组肺组织损伤明显减轻；免疫组化结果显示，LPS组小鼠肺组织VE—cadherin表达明显降低，ROCK2表达明显增高（均P〈0．05），而UTI干预后，VE—cadherin表达明显增加，ROCK表达明显下降（均P〈0．05）。结论UTI能够剂量依赖性地降低LPS所致的肺毛细血管通透性增加，从而改善脓毒症小鼠肺损伤，这一作用可能与UTI抑制Rho／ROCK信号通路的激活有关。

英文摘要：

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 10^4 U/kg and 10^5 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.