Testosterone deficiency promotes the development of pulmonary emphysema in orchiectomized mice exposed to elastase
Testosterone deficiency promotes the development of pulmonary emphysema in orchiectomized mice exposed to elastase
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DOI：
10.1016/j.bbrc.2021.04.051
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发表时间：
2021-04-24
影响因子：
3.1
通讯作者：
Yamauchi, Atsushi
中科院分区：
文献类型：
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作者：
Aono, Kentaro;Matsumoto, Junichi;Yamauchi, Atsushi
在患有慢性阻塞性肺疾病（COPD）的男性患者中通常观察到睾酮缺乏，COPD的特征在于气道的慢性炎症和肺气肿。虽然临床试验表明睾酮替代治疗可以改善COPD患者的呼吸功能，但睾酮在COPD发病机制中的作用尚不清楚。本研究的目的是探讨睾酮缺乏对暴露于猪胰弹性蛋白酶（PPE）的睾丸切除（ORX）小鼠肺气肿发生的影响。ORX小鼠在吸入PPE后21天比非ORX小鼠发生更严重的肺气肿变化。补充丙酸睾酮可显着减少PPE诱导的ORX小鼠肺气肿变化。PPE暴露也增加了接受ORX和假手术的小鼠支气管肺泡灌洗液（BALF）中中性粒细胞和T细胞的数量。ORX小鼠BALF中T细胞计数显著高于假手术小鼠。补充睾酮可减少T细胞向BALF中的浸润，并减轻ORX小鼠肺气肿的变化。我们的研究结果表明，睾酮，男性特异性激素，可能通过调节T细胞介导的免疫抑制肺气肿的发展。(c)2021爱思唯尔公司All rights reserved.
Testosterone deficiency is commonly observed in male patients with chronic obstructive pulmonary disease (COPD), which is characterized by chronic inflammation of the airways and pulmonary emphysema. Although clinical trials have indicated that testosterone replacement therapy can improve respiratory function in patients with COPD, the role of testosterone in the pathogenesis of COPD remains unclear. The aim of this study was to explore the effect of testosterone deficiency on the development of pulmonary emphysema in orchiectomized (ORX) mice exposed to porcine pancreatic elastase (PPE). ORX mice developed more severe emphysematous changes 21 d after PPE inhalation than non-ORX mice. Testosterone propionate supplementation significantly reduced PPE-induced emphysematous changes in ORX mice. PPE exposure also increased the number of neutrophils and T cells in bronchoalveolar lavage fluid (BALF) of mice that had undergone ORX and sham surgery. T cell counts were significantly higher in the BALF of ORX mice than of sham mice. Testosterone supplementation reduced the infiltration of T cells into BALF and alleviated emphysematous changes in the lungs of ORX mice. Our findings suggest that testosterone, a male-specific hormone, may suppress the development of pulmonary emphysema through the regulation of T cell-mediated immunity.(c) 2021 Elsevier Inc. All rights reserved.