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ORIGINAL ARTICLE
Year : 2018  |  Volume : 131  |  Issue : 10  |  Page : 1167-1173

Protectin DX Exhibits Protective Effects in Mouse Model of Lipopolysaccharide-Induced Acute Lung Injury


1 Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Department of Critical Care Medicine, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022; Department of Cardiac Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
2 Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Department of Critical Care Medicine, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China

Correspondence Address:
Dr. You Shang
Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0366-6999.227618

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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.

 

 Abstract in Chinese

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。



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