Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao 150081, China.
Exp Biol Med (Maywood). 2018 Jan;243(1):87-95. doi: 10.1177/1535370217740852. Epub 2017 Nov 2.
Mechanical ventilation is extensively used to treat patients with lung injury but may result in ventilator-induced lung injury (VILI). The present study investigated the protective effect of alpha 1-antitrypsin (AAT) on VILI. Adult male rats were subjected to sham, ventilation + saline, or ventilation + AAT treatment and lung injuries were evaluated. Peripheral blood and bronchoalveolar lavage fluid (BALF) were obtained to assess systemic and local inflammatory responses, respectively. Mechanical ventilation resulted in lung injury, as evidenced by histological abnormalities as well as elevations in PaO/FiO ratio, the wet-to-dry weight ratio, and the BALF level of proteins. The intravenous administration of AAT significantly improved these parameters of lung function, suggesting a protective role of AAT in VILI. Mechanistically, ventilator-induced inflammation was effectively reduced by AAT, as evidenced by decreases in BALF neutrophil counts, BALF cytokines, and serum adhesion factors. In contrast, anti-inflammatory interleukin-10 in BALF was increased in response to AAT. AAT treatment also inhibited the expression of nuclear factor-κB, Bax, and cleaved caspase-3 while promoting Bcl-2 expression in ventilator-injured lung tissues. AAT treatment can ameliorate VILI by inhibiting inflammatory mediator production and apoptosis. Impact statement Mechanical ventilation has been commonly used to treat patients with lung injury but may result in ventilator-induced lung injury (VILI). Few effective treatment options are currently available to reduce VILI. Alpha 1-antitrypsin (AAT) is an inhibitor of serine protease with anti-inflammatory and antiapoptotic properties, suggesting a possible role in attenuating lung injury. The present study demonstrates that AAT inhibits the development of VILI by modulating inflammation- and apoptosis-related protein expression. Therefore, AAT may be a novel therapeutic agent for acute respiratory distress syndrome patients undergoing mechanical ventilation.
机械通气广泛用于治疗肺损伤患者，但可能导致呼吸机相关性肺损伤（VILI）。本研究探讨了α 1-抗胰蛋白酶（AAT）对 VILI 的保护作用。成年雄性大鼠接受假手术、通气+盐水或通气+AAT 处理，并评估肺损伤。分别从外周血和支气管肺泡灌洗液（BALF）中获取样本，以评估全身和局部炎症反应。机械通气导致肺损伤，表现为组织学异常以及 PaO/FiO 比、湿重/干重比和 BALF 蛋白水平升高。静脉给予 AAT 可显著改善这些肺功能参数，表明 AAT 在 VILI 中具有保护作用。机制上，AAT 有效减轻了呼吸机诱导的炎症，表现为 BALF 中性粒细胞计数、BALF 细胞因子和血清黏附因子减少。相反，BALF 中的抗炎性白细胞介素-10 增加。AAT 治疗还抑制了核因子-κB、Bax 和 cleaved caspase-3 的表达，同时促进了呼吸机损伤肺组织中 Bcl-2 的表达。AAT 治疗通过抑制炎症介质的产生和细胞凋亡来改善 VILI。
