Background: Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis. Protectin DX (PDX), a pro-resolving lipid mediator, exhibits protective effects in ALI. Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide (LPS).
Methods: BALB/c mice were randomly divided into five groups: sham, LPS, LPS plus 1 ng of PDX (LPS + PDX-1 ng), LPS plus 10 ng of PDX (LPS + PDX-10 ng), and LPS plus 100 ng of PDX (LPS + PDX-100 ng). Bronchoalveolar lavage fluids (BALFs) were collected after 24 h, and total cells, polymorphonuclear leukocytes, monocyte-macrophages, and lymphocytes in BALF were enumerated. The concentration of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein (MIP)-1α, and MIP-2 in BALF was determined, and histopathological changes of the lung were observed. The concentration of protein in BALF and lung wet/dry weight ratios were detected to evaluate pulmonary edema. After determining the optimal dose of PDX, neutrophil-platelet interactions in whole blood were evaluated by flow cytometry.
Results: The highest dose of PDX (100 ng/mouse) failed to provide pulmonary protective effects, whereas lower doses of PDX (1 ng/mouse and 10 ng/mouse), especially 1 ng PDX, alleviated pulmonary histopathological changes, mitigated LPS-induced ALI and pulmonary edema, inhibited neutrophil infiltration, and reduced pro-inflammatory mediator (IL-1β, IL-6, TNF-α, and MIP-1α) levels. Meanwhile, 1 ng PDX exhibited pro-resolving functions in ALI including upregulation of monocyte-macrophage numbers and anti-inflammatory mediator IL-10 levels. The flow cytometry results showed that PDX could inhibit neutrophil-platelet interactions in ALI.
Conclusion: PDX exerts protective effects in LPS-induced ALI by mitigating pulmonary inflammation and abrogating neutrophil-platelet interactions.
保护素DX对脂多糖诱导的急性肺损伤的保护效应摘要背景：急性肺损伤（ALI）在临床上死亡率高预后差。保护素DX (PDX)，一种促炎症消退介质，发挥着对急性肺损伤的保护效应。本实验主要探讨PDX在LPS诱导的急性肺损伤中的作用及其相关机制。 方法：BALB/c小鼠被随机分到5个组：sham组，LPS组，LPS+1ng PDX组（LPS+PDX-1ng）, LPS+10ng PDX组 (LPS+PDX-10ng), LPS+100ng PDX组 (LPS+PDX-100ng)。24小时后收集小鼠支气管肺泡灌洗液（BALF），计数BALF中总细胞数、中性粒细胞数、单核细胞-巨噬细胞数和淋巴细胞数。测定BALF中炎症因子IL-1β, IL-6, TNF-a, IL-10, MIP-1a和MIP-2。观察肺病理学变化，测定BALF中蛋白浓度和肺组织湿/干重比用于评价肺水肿。以此确定PDX的最佳剂量，并用流式细胞术分析中性粒细胞-血小板相互作用。 结果：高剂量PDX（100ng/只）不能发挥对肺的保护效应，然而低剂量的PDX（1 ng/只，10 ng/只），尤其是1 ng PDX，能减轻肺病理改变，减缓LPS诱导的急性肺损伤和肺水肿，抑制中性粒细胞渗出，下调促炎因子（IL-1β, IL-6, TNF-a和MIP-a）。同时1 ng PDX在急性肺损伤中发挥促炎症消退的作用，包括上调单核-巨噬细胞比例和抗炎因子IL-10。流式细胞术结果显示PDX能抑制急性肺损伤中性粒细胞-血小板相互作用。 结论：PDX通过减轻肺部炎症和中性粒细胞-血小板相互作用发挥对LPS诱导的急性肺损伤的保护效应。.
Keywords: Acute Lung Injury; Blood Platelets; Lipopolysaccharide; Neutrophils; Protectin DX.