Abstract：
Childhood asthma, a common chronic childhood disease, leads to high mortality and morbidity in the world. Airway smooth muscle cells (ASMCs) is a group of multifunctional cells that has been found to be correlated with the pathogenesis of asthma. Astragaloside IV (AS-IV) is a compound extracted from Astragalus membranaceus, which has the anti-asthmatic effect. However, the role of molecular mechanisms regulated by AS-IV in the biological processes of ASMCs in asthma remains unclear. Our current study aims to investigate the downstream molecular mechanism of AS-IV in modulating the aberrant proliferation and pyroptosis of ASMCs in asthma. At first, we determined that the viability of ASMCs could be efficiently suppressed by AS-IV treatment (200 μM). Moreover, AS-IV promoted the pyroptosis and suppressed PDGF-BB-induced aberrant proliferation. Through mechanism investigation, we confirmed that AS-IV could suppress high mobility group box 1 (HMGB1) expression and prevent it from entering the cytoplasm. Subsequently, AS-IV blocked the interaction between HMGB1 and advanced glycosylation end product-specific receptor (RAGE) to inactivate NF-κB pathway. Finally, in vivo experiments demonstrated that AS-IV treatment can alleviate the lung inflammation in asthma mice. Collectively, AS-IV alleviates asthma and suppresses the pyroptosis of AMSCs through blocking HMGB1/RAGE axis to inactivate NF-κB pathway.
摘要：
儿童哮喘,一种常见的慢性儿童疾病，导致世界上高死亡率和发病率。气道平滑肌细胞（ASMC）是一组多功能细胞，已发现与哮喘的发病机理有关。黄芪甲苷（AS-IV）是从黄芪中提取的化合物，具有抗哮喘作用。然而,AS-IV调节的分子机制在哮喘ASMC生物学过程中的作用尚不清楚.我们目前的研究旨在探讨AS-IV调节哮喘ASMC异常增殖和焦亡的下游分子机制。起初,我们确定ASMC的活力可以通过AS-IV处理(200μM)有效抑制。此外，AS-IV促进焦亡并抑制PDGF-BB诱导的异常增殖。通过机制调查，我们证实AS-IV可以抑制高迁移率族蛋白1（HMGB1）的表达并阻止其进入细胞质。随后，AS-IV阻断HMGB1与高级糖基化终产物特异性受体（RAGE）之间的相互作用，从而使NF-κB通路失活。最后,体内实验表明，AS-IV治疗可以减轻哮喘小鼠的肺部炎症。总的来说，AS-IV通过阻断HMGB1/RAGE轴使NF-κB通路失活，减轻哮喘和抑制AMSCs的焦亡。
