中性粒细胞明胶酶相关脂质运载蛋白在小鼠呼吸机所致肺损伤模型中的表达

 目的：中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是25 kD大小的脂质运载蛋白超家族一员。我们通过观察NGAL在小鼠呼吸机所致肺损伤(VILI)模型中不同机械通气策略对其表达的影响，探讨NGAL是否为VILI新的生物标志物。方法：采用不同的机械通气策略作用于小鼠，构建不同的急性肺损伤模型。利用实时定量RT-PCR观察小鼠肺组织NGAL mRNA的变化；利用Western blotting检测NGAL蛋白在肺组织、血清和支气管肺泡灌洗液（BALF）中的变化;采用免疫组化检测NGAL蛋白在损伤性通气肺组织中的空间定位。结果：不同的通气策略都能引起小鼠NGAL的表达升高，在损伤性通气策略组升高显著，高吸气末峰压组和大潮气量通气组NGAL mRNA和蛋白的表达明显升高，并且在肺组织的上皮细胞、血管内皮细胞和浸润的中性粒细胞中均有表达，提示NGAL是对机械刺激敏感的传感蛋白，可能参与了VILI的发病机制。结论：NGAL可能是一种新的、能早期判断VALI的生物标志物。监测血清和BALF中的NGAL水平有可能成为诊断VILI高危病人的有效工具。

Expression of neutrophil gelatinase-associated lipocalin in a mouse model of ventilator-induced lung injury

AIM：To elucidate the effects of mechanical ventilation on the expression of neutrophil gelatinase-associated lipocalin (NGAL) in mice for identifying NGAL as a novel and  potential biomarker for ventilator-induced lung injury (VILI). METHODS：Mice were subject to different strategies of mechanical ventilation to establish the mouse model of VILI. The changes of NGAL mRNA level were detected by real-time RT-PCR. At the same time, the protein levels of NGAL in the mouse lung tissues, serum and bronchoalveolar lavage fluid(BALF) were observed by Western blotting analysis. To evaluate the spatial localization of NGAL expression, triple immunohistochemical staining was conduced in the lung tissue samples from the mouse VILI model. RESULTS：NGAL expression was increased in different ventilation groups, and the levels were significantly elevated in VILI groups. The higher level of NGAL expression was observed in the high-peak inflation pressure group and high-volume group. These data implied an important role of NGAL as a sensor in mechanical stimulus and involved in the pathogenesis of VILI. CONCLUSION：NGAL is a potential and novel biomarker for the early prediction of VILI. Monitoring the changes of NGAL in serum and BALF is helpful to diagnose the patients with high risk  of VILI.