哮喘是一种以气道高反应性为特征的炎症性疾病,气道重塑,和气道炎症。近年来,哮喘的患病率一直在稳步增加,哮喘的发病机制因人而异。由于依从性差或抵抗力差,现有药物无法达到预期的治疗效果。因此,开发或筛选具有高疗效的哮喘治疗药物,低毒性,强特异性非常迫切。盐酸度洛西汀(DUX)是一种选择性5-羟色胺和去甲肾上腺素再摄取抑制剂,它主要用于治疗抑郁症,骨关节炎,和神经性疼痛。据报道,DUX具有潜在的抗感染作用,抗炎,镇痛药,抗氧化,和其他药理作用。然而,DUX是否对哮喘有一定影响尚不清楚.为了调查它,一系列离体和体内实验,包括生物张力测试,膜片钳,组织病理学分析,肺功能检测,氧化应激酶活性检测,和分子生物学实验,是在这项研究中设计的。我们发现DUX不仅可以通过调节L型电压依赖性Ca2通道(L-VDCC)和非选择性阳离子通道(NSCC)离子通道来放松高钾或ACh预收缩的气管平滑肌,而且还可以通过抗炎和缓解哮喘症状。PI3K/AKT/mTOR和Nrf2/HO-1信号通路调节的抗氧化反应。我们的数据表明DUX有望成为缓解或治疗哮喘的潜在新药。
Asthma is an inflammatory disease characterized by airway hyperresponsiveness, airway remodeling, and airway inflammation. In recent years, the prevalence of asthma has been increasing steadily and the pathogenesis of asthma varies from person to person. Due to poor compliance or resistance, existing drugs cannot achieve the desired therapeutic effect. Therefore, developing or screening asthma therapeutic drugs with high curative effects, low toxicity, and strong specificity is very urgent. Duloxetine HCl (DUX) is a selective serotonin and norepinephrine reuptake inhibitor, and it was mainly used to treat depression, osteoarthritis, and neuropathic pain. It was also reported that DUX has potential anti-infection, anti-inflammation, analgesic, antioxidative, and other pharmacological effects. However, whether DUX has some effects on asthma remains unknown. In order to investigate it, a series of ex vivo and in vivo experiments, including biological tension tests, patch clamp, histopathological analysis, lung function detection, oxidative stress enzyme activity detection, and molecular biology experiments, were designed in this study. We found that DUX can not only relax high potassium or ACh precontracted tracheal smooth muscle by regulating L-type voltage-dependent Ca2+ channel (L-VDCC) and nonselective cation channel (NSCC) ion channels but also alleviate asthma symptoms through anti-inflammatory and antioxidative response regulated by PI3K/AKT/mTOR and Nrf2/HO-1 signaling pathways. Our data suggests that DUX is expected to become a potential new drug for relieving or treating asthma.