sRAGE对脂多糖介导的小鼠急性肺损伤的保护作用

sRAGE affords protective roles against LPS-induced acute lung injury in mice

目的探讨可溶性晚期糖基化终末产物受体(sRAGE)对脂多糖(LPS)介导的小鼠急性肺损伤(ALI)的保护作用。方法向小鼠气管内滴注LPS建立ALI模型,造模后1h sRAGE组腹腔注射100μg sRAGE,于24 h留取标本,检测各组动物支气管肺泡灌洗液(BALF)中白细胞及中性粒细胞数量、蛋白浓度和肿瘤坏死因子(TNF)α-水平,并对肺组织进行病理学观察。结果LPS滴注24 h后,BALF中白细胞总数和中性粒细胞数量显著增加,蛋白含量升高,TNFα-释放增多,肺组织出现典型的ALI病理损害,sRAGE干预显著降低了BALF中白细胞及中性粒细胞数量、蛋白含量和TNFα-水平,减轻了LPS引起的肺组织病理改变。结论应用sRAGE阻止RAGE信号通过抑制LPS引起的肺内中性粒细胞聚集、肺毛细血管渗出、炎症因子TNFα-释放,对ALI发挥保护作用。

Objective To test the putative effects of sRAGE on LPS-induced acute lung injury （ALI） in mice. Methods Mouse models of ALI were made by intratracheal instillation of LPS. Mice in sRAGE group received intraperitoneal injection of 100 μg sRAGE 1 h after LPS challenge. Bronchnalvcolar lavage fluid from all the groups were collected 24 h after intratracheal instillation for cell counting, protein assay, TNF-α measurement and lungs were sam- pled for histopathology at the same time point. Results The leukocyte number, protein contents, TNF-α level in the BALF all significantly increased and the pathological changes were obvious 24 h after LPS challenge. Treatment to mice with recombinant sRAGE attenuated LPS-induced increases in neutrophil infiltration, protein leakage, production of TNF-α and development of pathological changes in the lung. Conclusion Blockade of RAGE signal by sRAGE plays protective roles against LPS-induced ALI by inhibiting increases in neutrophil accumulation, lung permeability and TNF-α production.