乌司他丁通过降低细胞间黏附分子-1的表达对急性肺损伤大鼠起保护作用

Protective effects of ulinastatin in lipopolysaccharide-induced acute lung injury by reducing the expression of. ICAM-I： experiment with rats

目的探讨乌司他丁保护脂多糖诱导急性肺损伤的作用机制。方法30只wistar大鼠随机均分成3组，A组：正常对照组；B组：注射脂多糖诱导急性肺损伤模型；C组：模型建立30分钟后静脉注射乌司他丁。6h后处死大鼠取其肺组织，行肺组织病理检测，测量湿干比，酶联免疫吸附测定法检测各组肺泡灌洗液中炎性因子IL-6和TNF-α的水平，Western-blotting检测肺组织ICAM-1和GAPDH蛋白含量。结果B组湿干比显著高于A组（P〈0．01），C组湿干比显著低于B组（P〈0．05）；B组肺泡灌洗液IL-6和TNF-α水平均显著高于A组（P〈0．01），而C组均显著低于B组（P〈0．01）；B组肺组织ICAM-1蛋白表达水平显著高于其他两组（均P〈0．01）。C组ICAM-I水平显著低于B组（P〈0．01），但高于A组（P〈0．05），GAPDH在三组中的表达量无显著差异。结论乌司他丁通过减轻肺组织炎性反应，降低ICAM-1在肺组织中的表达水平来发挥其保护作用。

Objective To investigate the mechanism of ulinastain in protecting the lung against acute lung injury （ALI） induced by lipopolysacharide （LPS）. Methods Thirty Wistar rats were randomly divided into 3 equal groups： Group A, normal control group, Group B, undergoing LPS injection to cause ALI, and Group C undergoing intravenous injection of ulinastatin 30 min after the model establishment. The rats were killed 6 hours later with their lungs taken out. Pathological examination was conducted. Wet to dry weight ratio was messured. Enzyme linked immunosorbent assay was used to test the levels of Inflammatory factors interleukin （IL）-6 and tumor necrosis factor-α （TNF-α） in the bronchoalveolar lavage fluid （BALF）, Western-blotting was used to detect the protein expression level of intercellular cell adhesion molecule-1 （ICAM-1） and glyceraldehyde-3-phosphate dehydrogenase （GAPDH）. Results The wet to dry weight ratio of Group B was significantly higher than that of Group A （P 〈0.01）, and the wet to dry weight ratio of Group C was significantly lower than that of Group B （P 〈0.05）. The histologicaal ferature of the lung tissue of Group A was normal, significant iInflammation phenomena were seen in the lung tissue of Group B, and the pathological changes were obviously milder in Group C in commparison with Group B. The BALF levels of IL-6 and TNF-α of Group B were both significantly higher than those of Group A （both P 〈 0.01）, and the BALF levels of I1-6 anf TNF-α of Group C were both significantly lower than those of Group B （both P 〈 0.01） . The ICAM-1 protein expression level in lung tissue of Group B was significantly higher than those of the other 2 groups （both P 〈 0.01）, and the ICAM-1 protein expression level in lung tissue of Group C was significantly lower than that of Group B （P 〈 0.01）, however, still significantly higher than that of Group A （P 〈0.05）, There was no significant differences in the protein expression level of GAPDH among these 3 groups. Conclusion Ulinastatin lessens inflammatory reaction of＇ lung tissue and decreases the expression of ICAM-1 in lung tissues, thus exerting its protective effects.