Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, Nangang District, Harbin, 150001, China.
Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, Nangang District, Harbin, 150001, China; Department of General Surgery, Xinxiang Medical University, No. 601, New Yan Road, Xinxiang 453000, China.
Biochem Biophys Res Commun. 2018 Sep 3;503(1):94-101. doi: 10.1016/j.bbrc.2018.05.186. Epub 2018 Jun 11.
Paraquat (PQ) is one of the most extensively used herbicides, possessing high toxicity for humans and animals. The lung is the main target organ by the poisoning of PQ resulting in acute lung injury. Nonetheless, molecular mechanisms underlying PQ-induced lung injury remain unclear. Here, we ask if angiopoietin-like protein 2 (Angptl2), a pro-inflammatory protein, contributes to inflammation that accelerates acute lung injury. The results indicated that abundant Angptl2 expression was observed in lung tissues of PQ-treated mice. Histological analysis revealed that PQ-induced histological changes were alleviated by Angptl2 knockout (Angptl2). Angptl2 in PQ-treated mice attenuated acute lung injury progression by reducing the number of total cells, total leukocytes, neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) and reducing inflammatory response through the inactivation of nuclear factor kappa B (NF-κB) pathway. Angptl2 reduced oxidative stress in PQ-treated mice, as evidenced by the enhanced superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) levels in serum or lung tissue samples, which was accompanied with increased expressions of nuclear respiratory factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1). PQ-induced fibrosis was also improved in Angptl2 mice by decreasing pulmonary transforming growth factor (TGF)-β1 expressions. In vitro, we found that Angptl2 knockdown-suppressed inflammation, oxidative stress and fibrosis was restored by increasing NF-κB activation in PQ-incubated A549 cells; however, the results above were significantly reversed by inactivating NF-κB using its inhibitor, Bay 11-7085 or LY2409881. Therefore, Angptl2 could provide therapeutic effects on PQ-induced acute lung injury through inhibiting inflammation, oxidative stress and fibrosis by regulating NF-κB pathway.
百草枯（PQ）是一种广泛使用的除草剂，对人类和动物具有高毒性。肺是 PQ 中毒导致急性肺损伤的主要靶器官。然而，PQ 诱导肺损伤的分子机制尚不清楚。在这里，我们想知道血管生成素样蛋白 2（Angptl2），一种促炎蛋白，是否有助于加速急性肺损伤的炎症反应。结果表明，在 PQ 处理的小鼠肺组织中观察到大量 Angptl2 表达。组织学分析表明，Angptl2 敲除（Angptl2）减轻了 PQ 诱导的组织学变化。Angptl2 在 PQ 处理的小鼠中通过减少支气管肺泡灌洗液（BALF）中的总细胞、总白细胞、中性粒细胞和巨噬细胞数量以及通过抑制核因子 kappa B（NF-κB）途径来减轻急性肺损伤进展。Angptl2 降低了 PQ 处理的小鼠的氧化应激，这表现为血清或肺组织样本中超氧化物歧化酶（SOD）活性的增强和丙二醛（MDA）水平的降低，同时核呼吸因子 2（Nrf-2）、血红素加氧酶-1（HO-1）和 NAD（P）H：醌氧化还原酶 1（NQO-1）的表达增加。Angptl2 还通过降低肺转化生长因子（TGF）-β1 的表达改善了 PQ 诱导的纤维化。在体外，我们发现 Angptl2 敲低抑制了炎症、氧化应激和纤维化，这一作用可通过增加 PQ 孵育的 A549 细胞中 NF-κB 的激活来恢复；然而，使用 NF-κB 抑制剂 Bay 11-7085 或 LY2409881 使其失活可以显著逆转上述结果。因此，Angptl2 可以通过调节 NF-κB 通路抑制炎症、氧化应激和纤维化，对 PQ 诱导的急性肺损伤发挥治疗作用。
Zotero 插件