Sakai Hitomi, Horiguchi Michiko, Akita Tomomi, Ozawa Chihiro, Hirokawa Mai, Oiso Yuki, Kumagai Harumi, Takeda Yoshito, Tachibana Isao, Maeda Norikazu, Yamashita Chikamasa
Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences (H.S., M.Ho., T.A., C.O., M.Hi., O.Y., H.K., C.Y.), and Fusion of Regenerative Medicine with DDS, Research Institute for Science and Technology (M.Ho., C.Y.), Tokyo University of Science, Chiba; Respiratory Medicine, Allergy and Rheumatic Diseases (Y.T., I.T., N.M.), and Department of Metabolism and Atherosclerosis (N.M.), Graduate School of Medicine, Osaka University, Osaka; Department of Medicine, Nissay Hospital, Nippon Life Saiseikai Public Interest Incorporated Foundation, Osaka (I.T.), Japan.
Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences (H.S., M.Ho., T.A., C.O., M.Hi., O.Y., H.K., C.Y.), and Fusion of Regenerative Medicine with DDS, Research Institute for Science and Technology (M.Ho., C.Y.), Tokyo University of Science, Chiba; Respiratory Medicine, Allergy and Rheumatic Diseases (Y.T., I.T., N.M.), and Department of Metabolism and Atherosclerosis (N.M.), Graduate School of Medicine, Osaka University, Osaka; Department of Medicine, Nissay Hospital, Nippon Life Saiseikai Public Interest Incorporated Foundation, Osaka (I.T.), Japan
J Pharmacol Exp Ther. 2017 Jun;361(3):501-505. doi: 10.1124/jpet.117.240515. Epub 2017 Apr 21.
Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease that causes widespread and irreversible alveolar collapse. Although COPD occurs worldwide, only symptomatic therapy is currently available. Our objective is the development of therapeutic agents to eradicate COPD. Therefore, we focused on 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid (Am80), which is a derivative of all- retinoic acid. We evaluated the effects of Am80 on alveolar repair in a novel COPD model of adiponectin-deficient mice. This mouse model has more symptoms similar to human COPD than the classic elastase-induced emphysema mouse model. Lung volume, computed tomography (CT) values, low-attenuation area ratios, and bone and fat mass were measured by CT. However, the administration of Am80 did not affect these results. To examine the degree of destruction in the alveoli, the mean linear intercept of the alveolar walls was calculated, and assessment of this value confirmed that there was a significant difference between the control (46.3 ± 2.3 m) and 0.5 mg/kg Am80-treated group (34.4 ± 1.7 m). All mice survived the treatment, which lasted for more than 6 months, and we did not observe any abnormalities in autopsies performed at 80 weeks of age. These results suggested that Am80 was effective as a novel therapeutic compound for the treatment of COPD.
慢性阻塞性肺疾病(COPD)是一种难治性肺部疾病,会导致广泛且不可逆的肺泡塌陷。尽管COPD在全球范围内都有发生,但目前只有对症治疗方法。我们的目标是开发根除COPD的治疗药物。因此,我们聚焦于4-[(5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基)氨基甲酰基]苯甲酸(Am80),它是全反式维甲酸的衍生物。我们在一种新型的脂联素缺乏小鼠COPD模型中评估了Am80对肺泡修复的影响。与经典的弹性蛋白酶诱导的肺气肿小鼠模型相比,这种小鼠模型具有更多与人类COPD相似的症状。通过计算机断层扫描(CT)测量肺容积、CT值、低衰减面积比以及骨骼和脂肪量。然而,给予Am80并未影响这些结果。为了检查肺泡的破坏程度,计算了肺泡壁的平均线性截距,对该值的评估证实对照组(46.3±2.3μm)与0.5mg/kg Am80治疗组(34.4±1.7μm)之间存在显著差异。所有小鼠在持续超过6个月的治疗中存活下来,并且在80周龄时进行的尸检中我们未观察到任何异常。这些结果表明,Am80作为一种新型治疗化合物对治疗COPD有效。