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Pyrrolidine dithiocarbamate and dexamethasone are novel treatments of Acute Exogenous Lipoid Pneumonia
Cytokine ( IF 3.7 ) Pub Date : 2020-09-01 , DOI: 10.1016/j.cyto.2020.155122
Dong-Shi Liang 1 , Ai-Rong Huang 1 , Miao-Miao Lin 1 , Xiao-Jiao Xia 1 , Yi-Mei Jin 1
Affiliation  

BACKGROUND Acute exogenous lipoid pneumonia (AELP) is characterized by pulmonary inflammation. This mainly occur in children who have ingested sewing machine oil or other mineral oils accidentally. Despite emerging evidences revealing that inhibiting inflammation improves acute exogenous lipoid pneumonia, the actual process of inhibiting inflammation remains unknown. This study aimed to evaluate the effects of PDTC and dexamethasone on AELP to gain insight into the mechanism of AELP. METHODS The experimental rats were randomly divided into 10 groups: NS control group (NS3 group, NS5 group), Oil inhalation group (AE3 group, AE5 group), PDTC intervention group (PDTC3 group, PDTC5 group), DXM intervention group (DXM3 group, DXM5 group), PDTC + DXM combined intervention group (PDTC + DXM3 group, PDTC + DXM 5 group). Enzyme-linked immunosorbent assay (ELISA) was used to determine concentrations of macrophage migration inhibitory factor (MIF), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) in bronchoalveolar lavage fluid (BALF) and serum samples. On the other hand, western blotting was used to measure the expression levels of nuclear factor-κB p65 (NF-κB p65) and b-cell leukemia 2 (Bcl-2) in the lungs. Hematoxylin and Eosin (H&E) staining was performed to evaluate changes in the lung tissue. The wet-to-dry lung weight ratio was subsequently used to determine the pulmonary edema of the lungs. RESULTS There were increased MIF levels in both serum and BALF samples of the AE group. Pyrrolidine dithiocarbamate (PDTC) and dexamethasone (DXM) independently and in combination reduced pulmonary inflammation induced by the sewing machine oil by regulating MIF expression. TNF-α and IL-6 levels in serum and BALF samples of the AE group were higher than those of the NS control animals. However, their levels decreased after treatment with either PDTC, DXM or PDTC + DXM. Similarly, NF-κBp65 expression increased after oil inhalation but decreased after treatment with either PDTC, DXM or PDTC + DXM. PDTC, DXM and PDTC + DXM treatment significantly reduced pulmonary inflammation and pulmonary edema of the lung tissue following induction of acute exogenous lipoid pneumonia. CONCLUSIONS Individual or combined use of PDTC and DXM can ameliorate pulmonary inflammation induced by inhalation of sewing machine oil by inhibiting the NF-κB pathway in young rats. These findings provide novel insights that will greatly contribute in treatment of AELP.

中文翻译:

吡咯烷二硫代氨基甲酸酯和地塞米松是急性外源性类脂性肺炎的新疗法

背景急性外源性类脂性肺炎(AELP)的特征在于肺部炎症。这主要发生在不小心摄入了缝纫机油或其他矿物油的儿童身上。尽管新出现的证据表明抑制炎症可以改善急性外源性类脂性肺炎,但抑制炎症的实际过程仍然未知。本研究旨在评估PDTC和地塞米松对AELP的影响,以深入了解AELP的机制。方法将实验大鼠随机分为10组:NS对照组(NS3组、NS5组)、吸油组(AE3组、AE5组)、PDTC干预组(PDTC3组、PDTC5组)、DXM干预组(DXM3组) 、DXM5组)、PDTC+DXM联合干预组(PDTC+DXM3组、PDTC+DXM5组)。使用酶联免疫吸附试验 (ELISA) 测定支气管肺泡灌洗液 (BALF) 和血清样品中巨噬细胞迁移抑制因子 (MIF)、白介素-6 (IL-6) 和肿瘤坏死因子-α (TNFα) 的浓度。另一方面,蛋白质印迹用于测量肺中核因子-κB p65 (NF-κB p65) 和 b 细胞白血病 2 (Bcl-2) 的表达水平。进行苏木精和曙红 (H&E) 染色以评估肺组织的变化。随后使用湿与干肺重量比来确定肺的肺水肿。结果 AE 组的血清和 BALF 样本中 MIF 水平均升高。吡咯烷二硫代氨基甲酸酯 (PDTC) 和地塞米松 (DXM) 独立和组合通过调节 MIF 表达减少由缝纫机油诱导的肺部炎症。AE 组血清和 BALF 样品中 TNF-α 和 IL-6 水平高于 NS 对照动物。然而,在用 PDTC、DXM 或 PDTC + DXM 治疗后,它们的水平下降。类似地,吸入油后 NF-κBp65 表达增加,但在用 PDTC、DXM 或 PDTC + DXM 处理后降低。PDTC、DXM 和 PDTC + DXM 治疗显着减少了诱导急性外源性类脂性肺炎后肺组织的肺部炎症和肺水肿。结论 PDTC与DXM单独或联合使用可通过抑制NF-κB通路来改善吸入缝纫机油所致的肺部炎症。这些发现提供了新的见解,将极大地促进 AELP 的治疗。
更新日期:2020-09-01
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