噻托溴铵在重度气道阻塞的实验模型——阻力呼吸过程中发挥抗炎作用。
Tiotropium bromide exerts anti-inflammatory effects during resistive breathing, an experimental model of severe airway obstruction.
作者信息
Toumpanakis Dimitrios, Loverdos Konstantinos, Tzouda Vassiliki, Vassilakopoulou Vyronia, Litsiou Eleni, Magkou Christina, Karavana Vassiliki, Pieper Michael, Vassilakopoulos Theodoros
机构信息
First Critical Care Department, Pulmonary Unit, National and Kapodistrian University of Athens Medical School, Evangelismos General Hospital.
George P. Livanos and Marianthi Simou Laboratories, Thorax Foundation.
出版信息
Int J Chron Obstruct Pulmon Dis. 2017 Jul 28;12:2207-2220. doi: 10.2147/COPD.S137587. eCollection 2017.
INTRODUCTION
Resistive breathing (RB), a hallmark of obstructive airway diseases, is characterized by strenuous contractions of the inspiratory muscles that impose increased mechanical stress on the lung. RB is shown to induce pulmonary inflammation in previous healthy animals. Tiotropium bromide, an anticholinergic bronchodilator, is also shown to exert anti-inflammatory effects. The effect of tiotropium on RB-induced pulmonary inflammation is unknown.
METHODS
Adult rats were anesthetized, tracheostomized and breathed spontaneously through a two-way non-rebreathing valve. Resistances were connected to the inspiratory and/or expiratory port, to produce inspiratory resistive breathing (IRB) of 40% or 50% / (40% and 50% IRB), expiratory resistive breathing (ERB) of 60% / (60% ERB) or combined resistive breathing (CRB) of both 40% / and 60% / (40%/60% CRB). Tiotropium aerosol was inhaled prior to RB. After 6 h of RB, mechanical parameters of the respiratory system were measured and bronchoalveolar lavage (BAL) was performed. IL-1β and IL-6 protein levels were measured in lung tissue. Lung injury was estimated histologically.
RESULTS
In all, 40% and 50% IRB increased macrophage and neutrophil counts in BAL and raised IL-1β and IL-6 lung levels, tissue elasticity, BAL total protein levels and lung injury score. Tiotropium attenuated BAL neutrophil number, IL-1β, IL-6 levels and lung injury score increase at both 40% and 50% IRB. The increase in macrophage count and protein in BAL was only reversed at 40% IRB, while tissue elasticity was not affected. In all, 60% ERB raised BAL neutrophil count and total protein and reduced macrophage count. IL-1β and IL-6 levels and lung injury score were increased. Tiotropium attenuated these alterations, except for the decrease in macrophage count and the increase in total protein level. In all, 40%/60% CRB increased macrophage and neutrophil count in BAL, IL-1β and IL-6 levels, tissue elasticity, total protein in BAL and histological injury score. Tiotropium attenuated the aforementioned alterations.
CONCLUSION
Tiotropium inhalation attenuates RB-induced pulmonary inflammation.
引言
抵抗性呼吸（RB）是阻塞性气道疾病的一个标志，其特征是吸气肌剧烈收缩，给肺部带来增加的机械应力。在先前健康的动物中，RB已被证明会诱发肺部炎症。噻托溴铵是一种抗胆碱能支气管扩张剂，也已被证明具有抗炎作用。噻托溴铵对RB诱导的肺部炎症的影响尚不清楚。
方法
成年大鼠麻醉后行气管切开术，并通过双向无重复呼吸阀自主呼吸。在吸气和/或呼气端口连接阻力器，以产生40%或50%的吸气抵抗性呼吸（IRB）/（40%和50% IRB）、60%的呼气抵抗性呼吸（ERB）/（60% ERB）或40%/和60%/的联合抵抗性呼吸（CRB）/（40%/60% CRB）。在进行RB之前吸入噻托溴铵气雾剂。RB 6小时后，测量呼吸系统的力学参数并进行支气管肺泡灌洗（BAL）。测量肺组织中白细胞介素-1β（IL-1β）和白细胞介素-6的蛋白质水平。通过组织学评估肺损伤。
结果
总体而言，40%和50%的IRB增加了BAL中的巨噬细胞和中性粒细胞计数，并提高了肺组织中IL-1β和IL-6水平、组织弹性、BAL总蛋白水平和肺损伤评分。噻托溴铵减轻了40%和50% IRB时BAL中性粒细胞数量、IL-1β、IL-6水平和肺损伤评分的增加。BAL中巨噬细胞计数和蛋白的增加仅在40% IRB时得到逆转，而组织弹性未受影响。总体而言，60%的ERB增加了BAL中性粒细胞计数和总蛋白，并减少了巨噬细胞计数。IL-1β和IL-6水平以及肺损伤评分增加。噻托溴铵减轻了这些改变，但巨噬细胞计数的减少和总蛋白水平的增加除外。总体而言，40%/60%的CRB增加了BAL中的巨噬细胞和中性粒细胞计数、IL-1β和IL-6水平、组织弹性、BAL总蛋白和组织学损伤评分。噻托溴铵减轻了上述改变。
结论
吸入噻托溴铵可减轻RB诱导的肺部炎症。
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