Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. However, no drugs can regenerate lung tissue in COPD patients, and differentiation-inducing drugs that can effectively treat damaged alveoli are needed. In addition, the presence of systemic comorbidities is also considered problematic. Our previous study revealed that a retinoic acid derivative improved emphysema in elastase-induced COPD model mice at a dose of 1.0 mg/kg, whereas 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) showed an emphysema-improving effect in the same model at 0.1 μg/kg. Elastase-induced COPD model mice do not exhibit a systemic disease state, so evaluation in a model that better reflects the human disease state is considered necessary. To solve this problem, we focused on the adiponectin-deficient mouse and examined the effects of 1,25(OH)2D3 on alveolar regeneration. Fifty-week-old adiponectin-deficient mice were treated with 1,25(OH)2D3 (0.1 μg/kg) twice a week, for 30 weeks. The effects of pulmonary administration on alveolar repair were evaluated according to the distance between alveolar walls (Lm values) and computed tomography (CT) parameters. Bone density was evaluated based on CT. The administration of 1,25(OH)2D3 was confirmed to show a significant therapeutic effect. The Lm values in the control and 1,25(OH)2D3-treated groups were 98 ± 4 μm and 63 ± 1 μm, respectively. However, on CT, the average CT value and % of low attenuation area showed no significant change. In adiponectin-deficient mice, the reduction of bone density (cortical, spongy, and total bone), which is a systemic symptom of COPD, was significantly suppressed by 1,25(OH)2D3 at 80 weeks of age. The present study suggests that 1,25(OH)2D3 could be a potential candidate drug that may provide a radical cure for the lung disease and comorbidities of COPD patients. This work can lead to the development drugs that may provide a radical cure for COPD.

中文翻译：

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1α，25-二羟基维生素D3对脂联素缺乏症小鼠肺泡修复和骨量的影响。

慢性阻塞性肺疾病（COPD）是全球范围内的主要死亡原因。然而，没有药物能够使COPD患者的肺组织再生，因此需要能够有效治疗受损肺泡的分化诱导药物。此外，系统性合并症的存在也被认为是有问题的。我们先前的研究表明，视黄酸衍生物以1.0 mg / kg的剂量可改善弹性蛋白酶诱导的COPD模型小鼠的肺气肿，而1α，25-二羟基维生素D3（1,25（OH）2D3）则可改善肺气肿。相同型号的剂量为0.1μg/ kg。弹性蛋白酶诱导的COPD模型小鼠没有表现出全身性疾病状态，因此需要在模型中进行评估以更好地反映人类疾病状态。为了解决这个问题，我们集中研究了缺乏脂联素的小鼠，并研究了1的作用。25（OH）2D3对肺泡再生的影响。五十周大的脂联素缺乏症小鼠每周两次接受1,25（OH）2D3（0.1μg/ kg）处理，持续30周。根据肺泡壁之间的距离（Lm值）和计算机断层扫描（CT）参数评估肺部给药对肺泡修复的影响。基于CT评估骨密度。确认施用1,25（OH）2D3具有明显的治疗作用。对照组和1,25（OH）2D3处理组的Lm值分别为98±4μm和63±1μm。但是，在CT上，平均CT值和低衰减区域的百分比没有显着变化。在缺乏脂联素的小鼠中，作为COPD的全身症状的骨密度（皮质，海绵状和全骨）的降低在80周龄时被1,25（OH）2D3显着抑制。本研究表明1,25（OH）2D3可能是潜在的候选药物，可以为COPD患者的肺部疾病和合并症提供根本性的治疗方法。这项工作可以导致开发药物，可以为COPD带来根本性的治愈。