Yin Ning, Peng Zhendan, Li Bin, Xia Jiangyan, Wang Zhen, Yuan Jing, Fang Lei, Lu Xinjiang
Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University Nanjing 210009, Jiangsu, China.
Am J Transl Res. 2016 May 15;8(5):2033-46. eCollection 2016.
Nucleotide-binding domains and leucine-rich repeat (NLR) pyrin domains containing 3 (NLRP3) inflammasome are highly involved in the pathogenesis of acute lung injury (ALI) wherein alveolar macrophages (AMs) play a crucial role. Isoflurane (ISO) has been shown to attenuate ALI. However, the inhibitory effects of ISO on NLRP3 activation in lipopolysaccharide (LPS)-induced ALI remain unknown. Here, we showed that 1.4% ISO post-treatment reduced LPS-induced body weight loss, pulmonary histopathological injury, edema, and vascular permeability in rats. ISO attenuated LPS-triggered inflammation, as evidenced by reductions in the number of total cells, neutrophils, and macrophages, and the release of IL-1β and IL-18 in the bronchoalveolar lavage fluid. ISO treatment decreased the myeloperoxidase activity, F4/80-positive cells, and the mRNA expression of IL-1β and IL-18 in the lung tissues of LPS-treated rats. Mechanistically, ISO reduced NLRP3 activation and caspase-1 activity in a reactive oxygen species (ROS)-dependent manner. An in vitro study that ISO inhibited LPS-induced AM activation partly confirmed in vivo findings. Overall, these results indicate that ISO post-conditioning alleviated LPS-induced ALI possibly by inhibiting ROS-mediated NLRP3 inflammasome activation.
核苷酸结合结构域和富含亮氨酸重复序列（NLR）的含3个吡啉结构域（NLRP3）炎性小体高度参与急性肺损伤（ALI）的发病机制，其中肺泡巨噬细胞（AMs）起关键作用。异氟烷（ISO）已被证明可减轻ALI。然而，ISO对脂多糖（LPS）诱导的ALI中NLRP3激活的抑制作用尚不清楚。在此，我们表明，1.4% ISO后处理可减轻LPS诱导的大鼠体重减轻、肺组织病理学损伤、水肿和血管通透性。ISO减轻了LPS引发的炎症，支气管肺泡灌洗液中总细胞、中性粒细胞和巨噬细胞数量的减少以及IL-1β和IL-18的释放证明了这一点。ISO处理降低了LPS处理大鼠肺组织中的髓过氧化物酶活性、F4/80阳性细胞以及IL-1β和IL-18的mRNA表达。机制上，ISO以活性氧（ROS）依赖的方式降低NLRP3激活和半胱天冬酶-1活性。一项体外研究表明ISO抑制LPS诱导的AMs激活，部分证实了体内研究结果。总体而言，这些结果表明，ISO后处理可能通过抑制ROS介导的NLRP3炎性小体激活减轻LPS诱导的ALI。
