Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
Sci Rep. 2019 Oct 30;9(1):15601. doi: 10.1038/s41598-019-51648-1.
Patients with asthma with obesity experience severe symptoms, are unresponsive to conventional asthma treatment, and lack proper pharmacotherapy. Empagliflozin and dulaglutide, developed for diabetes, reduce weight, decrease insulin resistance, and exert additive effects. We evaluated the efficacy of empagliflozin, dulaglutide, and their combination on obesity-induced airway hyperresponsiveness (AHR) and lung fibrosis using a murine model. We assigned C57BL/6J mice to five groups: control, high-fat diet (HFD), and HFD with empagliflozin, dulaglutide, or both. Mice received a 12-week HFD, empagliflozin (5 days/week, oral gavage), and dulaglutide (once weekly, intraperitoneally). Both drugs significantly attenuated HFD-induced weight increase, abnormal glucose metabolism, and abnormal serum levels of leptin and insulin, and co-treatment was more effective. Both drugs significantly alleviated HFD-induced AHR, increased macrophages in bronchoalveolar lavage fluid (BALF), and co-treatment was more effective on AHR. HFD-induced lung fibrosis was decreased by both drugs alone and combined. HFD induced interleukin (IL)-17, transforming growth factor (TGF)-β1, and IL-1β mRNA and protein expression, which was significantly reduced by empagliflozin, dulaglutide, and their combination. Tumour necrosis factor (TNF)-α and IL-6 showed similar patterns without significant differences. HFD-enhanced T helper (Th) 1 and Th17 cell differentiation was improved by both drugs. Empagliflozin and dulaglutide could be a promising therapy for obesity-induced asthma and showed additive effects in combination.
肥胖症哮喘患者的症状严重，对常规哮喘治疗无反应，且缺乏适当的药物治疗。恩格列净和度拉糖肽是为治疗糖尿病而开发的药物，可减轻体重、降低胰岛素抵抗，并发挥协同作用。我们使用一种小鼠模型评估了恩格列净、度拉糖肽及其联合用药对肥胖诱导的气道高反应性（AHR）和肺纤维化的疗效。我们将 C57BL/6J 小鼠分为五组：对照组、高脂肪饮食（HFD）组和 HFD 加恩格列净组、HFD 加度拉糖肽组、HFD 加恩格列净和度拉糖肽组。小鼠接受 12 周的 HFD、恩格列净（每周 5 天，口服灌胃）和度拉糖肽（每周一次，腹腔内注射）。两种药物均显著减轻 HFD 诱导的体重增加、葡萄糖代谢异常、瘦素和胰岛素的异常血清水平，且联合治疗效果更佳。两种药物均显著缓解 HFD 诱导的 AHR，增加支气管肺泡灌洗液（BALF）中的巨噬细胞，且联合治疗对 AHR 的缓解作用更明显。两种药物单独和联合治疗均可减轻 HFD 诱导的肺纤维化。HFD 诱导的白细胞介素（IL）-17、转化生长因子（TGF）-β1 和 IL-1β mRNA 和蛋白表达显著降低，恩格列净、度拉糖肽及其联合治疗均可降低表达水平。肿瘤坏死因子（TNF）-α和 IL-6 也呈现相似的模式，但无显著差异。HFD 增强的 Th1 和 Th17 细胞分化均得到两种药物的改善。恩格列净和度拉糖肽可能是肥胖症哮喘的一种有前途的治疗方法，联合使用具有协同作用。
