Department of Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou Zhejiang, 324000, P.R. China.
Department of Laboratory Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou Zhejiang, 324000, P.R. China.
Exp Anim. 2022 Nov 10;71(4):481-490. doi: 10.1538/expanim.22-0018. Epub 2022 May 30.
Lung injury is one of the leading causes of death in sepsis. Abietic acid (AA) has demonstrated anti-inflammatory and bacteriostatic properties. Herein, we established a mouse model of sepsis by cecal ligation and puncture, and intraperitoneally injected AA to treat. Lung injury was assessed by H&E staining and the inflammation in bronchoalveolar lavage fluid (BALF) were assessed by counting the number of inflammatory cells and detecting the content of inflammatory factors. Meanwhile, we also designed to study the effect of AA on lipopolysaccharide (LPS)-induced inflammatory response and macrophage marker gene expression in RAW264.7 cells in vitro. In this study, we found that AA inhibited LPS-induced secretion of inflammatory mediators (IL-1β, TNF-α, IL-6 and MIP-2), and decreased the expression of M1 macrophage e markers (CD16 and iNOS) and p-p65 protein, while increased the expression of M2 macrophage markers (CD206 and Arg-1) in RAW264.7 cells in vitro. In vivo, the therapy of AA not only rescued septic animals, but also attenuated lung injury in sepsis mice. Moreover, AA decreased the number of total cells, neutrophils and macrophages, the conceration of total protein, and the levels of inflammatory mediators in BALF of sepsis mice. Further, we found that AA inhibited M1 macrophage polarization and blocked nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in BALF of sepsis mice. In conclusion, Abietic acid attenuates sepsis-induced lung injury, and its mechanism may be related to reducing inflammation by inhibiting NF-κB signaling to inhibit M1 macrophage polarization.
肺损伤是脓毒症死亡的主要原因之一。枞酸（AA）具有抗炎和抑菌作用。在此，我们通过盲肠结扎和穿孔建立了脓毒症小鼠模型，并通过腹腔注射 AA 进行治疗。通过 H&E 染色评估肺损伤，通过计数炎症细胞数量和检测炎症因子含量评估支气管肺泡灌洗液（BALF）中的炎症。同时，我们还设计了研究 AA 对体外 RAW264.7 细胞中脂多糖（LPS）诱导的炎症反应和巨噬细胞标记基因表达的影响。在这项研究中，我们发现 AA 抑制 LPS 诱导的炎症介质（IL-1β、TNF-α、IL-6 和 MIP-2）分泌，并降低 M1 巨噬细胞标记物（CD16 和 iNOS）和 p-p65 蛋白的表达，同时增加 RAW264.7 细胞中 M2 巨噬细胞标记物（CD206 和 Arg-1）的表达。在体内，AA 的治疗不仅挽救了脓毒症动物，还减轻了脓毒症小鼠的肺损伤。此外，AA 降低了脓毒症小鼠 BALF 中总细胞、中性粒细胞和巨噬细胞的数量，总蛋白浓度以及炎症介质的水平。此外，我们发现 AA 抑制了 M1 巨噬细胞极化，并阻断了核因子 kappa-轻链增强子的激活 B 细胞（NF-κB）通路在脓毒症小鼠的 BALF 中。总之，枞酸减轻脓毒症引起的肺损伤，其机制可能与通过抑制 NF-κB 信号通路抑制 M1 巨噬细胞极化来减轻炎症有关。
