Shin Na-Rae, Park Sung-Hyeuk, Ko Je-Won, Cho Young-Kwon, Lee In-Chul, Kim Jong-Choon, Shin In-Sik, Kim Joong-Sun
College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, South Korea.
College of Health Sciences, Cheongju University, Cheongju, South Korea.
Front Pharmacol. 2018 Aug 8;9:906. doi: 10.3389/fphar.2018.00906. eCollection 2018.
Lobeglitazone (LB) is a novel agonist of peroxisome proliferator-activated receptor (PPAR)-α and γ that was developed as a drug to treat diabetes mellitus. We explored the ameliorative effects of LB on allergic asthma using a murine model of ovalbumin (OVA)-induced asthma. To boost the immune response of animals, OVA sensitization was performed on days 0 and 14. LB (250 or 500 μg/kg) was administered by oral gavage on days 18 to 23, and the OVA challenge was performed using an ultrasonic nebulizer on days 21 to 23. Plethysmography showed airway hyperresponsiveness (AHR) on day 24. LB treatment effectively decreased inflammatory cell recruitment, T-helper type 2 cytokines in the bronchoalveolar lavage fluid, and immunoglobulin (Ig) E in the serum of the animals with OVA-induced asthma, which was accompanied by a marked reduction in AHR. It also decreased airway inflammation, mucus hypersecretion, phosphorylation of nuclear transcription factor-kappa-B (NF-κB), and expression of activating protein (AP)-1 and mucin 5AC (MUC5AC). Overall, LB effectively attenuated the pathophysiological changes of asthma and its effects appear related to a reduction in the phosphorylation of NF-κB and the expression of AP-1. Thus, our results suggest that LB has a potential to treat allergic asthma.
罗格列酮（LB）是一种新型的过氧化物酶体增殖物激活受体（PPAR）-α和γ激动剂，被开发用作治疗糖尿病的药物。我们使用卵清蛋白（OVA）诱导的哮喘小鼠模型探讨了LB对过敏性哮喘的改善作用。为增强动物的免疫反应，在第0天和第14天进行OVA致敏。在第18至23天通过口服灌胃给予LB（250或500μg/kg），并在第21至23天使用超声雾化器进行OVA激发。体积描记法显示在第24天出现气道高反应性（AHR）。LB治疗有效减少了OVA诱导哮喘动物支气管肺泡灌洗液中的炎症细胞募集、2型辅助性T细胞细胞因子以及血清中的免疫球蛋白（Ig）E，同时AHR显著降低。它还减少了气道炎症、黏液分泌过多、核转录因子-κB（NF-κB）的磷酸化以及激活蛋白（AP）-1和黏蛋白5AC（MUC5AC）的表达。总体而言，LB有效减轻了哮喘的病理生理变化，其作用似乎与NF-κB磷酸化和AP-1表达的降低有关。因此，我们的结果表明LB有治疗过敏性哮喘的潜力。
