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在急性嗜中性粒细胞性哮喘小鼠模型中,噻托溴铵比皮质类固醇具有更强的作用。

Tiotropium Bromide Has a More Potent Effect Than Corticosteroid in the Acute Neutrophilic Asthma Mouse Model.

作者信息

An Tai Joon, Kim Ji Hye, Park Chan Kwon, Yoon Hyoung Kyu

机构信息

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

出版信息

Tuberc Respir Dis (Seoul). 2022 Jan;85(1):18-24. doi: 10.4046/trd.2021.0118. Epub 2021 Nov 2.

Abstract

BACKGROUND

Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is a bronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthma treatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect of TIO on NeuA compared to that of corticosteroids.

METHODS

C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilic inflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and 23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL) and lung homogenates, and lung tissue histopathology were compared between the two groups.

RESULTS

Neutrophil counts, T helper 2 cells (TH2)/TH17 cytokines, and pro-inflammatory cytokine in BAL fluids were elevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluids than the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group but elevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in the TIO group than in the NeuA group (all p<0.05).

CONCLUSION

TIO showed more potent effects than DEX in improving airway inflammation and attenuating airway resistance in NeuA.

摘要

背景

嗜中性粒细胞性哮喘(NeuA)通常对皮质类固醇耐药。噻托溴铵(TIO)是一种支气管扩张剂,在哮喘治疗中用作吸入性皮质类固醇和长效β2受体激动剂的附加治疗药物。然而,TIO在NeuA中的作用尚不完全清楚。因此,本研究的目的是评估TIO与皮质类固醇相比对NeuA的影响。

方法

用卵清蛋白和脂多糖致敏C57BL/6雌性小鼠以诱导嗜中性粒细胞炎症。在第14、17、20和23天给予地塞米松(DEX)。在第21、22和23天吸入TIO。在第24天处死小鼠。比较两组之间的气道高反应性、支气管肺泡灌洗(BAL)液和肺匀浆中细胞因子水平以及肺组织病理学。

结果

NeuA组BAL液中的中性粒细胞计数、辅助性T细胞2(TH2)/TH17细胞因子和促炎细胞因子升高。TIO组BAL液中的总细胞数、中性粒细胞计数和嗜酸性粒细胞计数低于DEX组(分别为p<0.001、p<0.05和p<0.001)。TIO组气道阻力降低,而NeuA组气道阻力升高(p<0.001)。TIO组BAL液中的总蛋白、白细胞介素(IL)-5和IL-17A水平低于NeuA组(均p<0.05)。

结论

在改善NeuA的气道炎症和减轻气道阻力方面,TIO比DEX显示出更强的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807a/8743638/e8dce6b7cd31/trd-2021-0118f1.jpg

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