白介素17对急性肺损伤时肺水肿液清除的影响

Role of interleukin-17 in alveolar fluid clearance in mice with acute lung injury

目的探讨白介素17(IL-17)对急性肺损伤(ALI)小鼠肺水清除的影响及可能机制。方法 IL-17基因敲除鼠和野生型C57BL/6鼠各16只,随机各等分为两组(一共4组,每组8只),分别经气道给与磷酸缓冲盐溶液和脂多糖(LPS)干预,给药48 h后处死。比较各组肺湿干质量比(W/D)、支气管肺泡灌洗液中白介素8(IL-8)水平和肺组织钠通道(ENa C)蛋白表达情况。并采用HE染色观察肺组织病理改变,免疫组化法了解肝激酶B1(LKB1)表达差异。结果与接受LPS干预的野生型鼠比较,IL-17敲除型鼠在接受LPS处理后W/D由9.739±3.3降至5.351±0.56,IL-8由67.50±7.33 pg/m L降至41.00±3.16 pg/m L,差异有统计学意义。病检结果提示IL-17敲除型鼠肺泡腔内水肿液聚集减少,肺损伤评分显著降低。Western blotting和免疫组化结果示接受LPS刺激的IL-17敲除型鼠ENa C表达更多,LKB1丢失相对较少。结论敲除IL-17不仅可以减轻ALI小鼠肺组织炎症程度,还可以减少ENa C蛋白丢失,促进肺水清除,其保护作用可能与LKB1有关。

Objective To investigate the role of interleukin-17(IL-17) in alveolar fluid clearance in mice with acute lung injury(ALI) and explore the possible mechanism. Methods Sixteen IL-17-knockout mice and 16 wild-type mice were both randomized for intratracheal instillation of PBS(control) on lipopolysaccharide(LPS) to induce ALI. Forty-eight hours after the treatments, the wet-dry ratio(W/D) of the lungs, IL-8 in the bronchoalveolar lavage fluid(BALF) and histopathological changes of the lung tissues were examined. The expressions of epithelial sodium channel α subunit(α-ENa C) was detected with Western blotting and liver kinase B1(LKB1) was detected with immunohistochemistry. Results Compared with wild-type mice treated with LPS, IL-17 knockout mice showed significantly decreased W/D of the lungs(9.739±3.3 vs 5.351±0.56) and IL-8level in the BALF(67.50 ± 7.33 vs 41.00 ± 3.16 pg/m L) following LPS challenge. Pathological examination revealed reduced alveolar edema fluid aggregations and lower lung injury score in IL-17 knockout mice with also higher expression levels of ENa C and LKB1 compared with the wild-type mice. Conclusion Knocking out IL-17 in mice not only alleviates inflammation of the lung tissue following ALI but also reduces the loss of ENa C protein and promotes alveolar fluid clearance, mechanism of which is probably associated with LKB1.