Sodium tanshinone IIA sulfonate stimulated Cl− secretion in mouse trachea

Sodium tanshinone IIA sulfonate (STS) is a derivate of tanshinone IIA, a lipophilic compound in Salvia miltiorrhiza. This study aimed to investigate the effect of STS on ion transport in mouse tracheal epithelium and the mechanisms underlying it. Short-circuit current (Isc) was measured to evaluate the effect of STS on transepithelial ion transport. Intracellular Ca2+ imaging was performed to observe intracellular Ca2+ concentration ([Ca2+]i) changes induced by STS in primary cultured mouse tracheal epithelial cells. Results showed that the apical application of STS at mouse trachea elicited an increase of Isc, which was abrogated by atropine, an antagonist of muscarinic acetylcholine receptor (mAChR). By removing ambient Cl− or applying blockers of Ca2+-activated Cl− channel (CaCC), the response of STS-induced Isc was suppressed. Moreover, STS elevated the [Ca2+]i in mouse tracheal epithelial cells. As a result, STS stimulated Cl− secretion in mouse tracheal epithelium via CaCC in an mAChR-dependent way. Due to the critical role of Cl− secretion in airway hydration, our findings suggested that STS may be used to ameliorate the airway dehydration symptom in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).丹参酮IIA磺酸钠（Sodium tanshinone IIA sulfonate，STS）是丹参中亲脂性成分丹参酮IIA的衍生物。本研究旨在探讨STS对小鼠气管上皮离子转运的影响及其潜在作用机制。为评估STS对跨上皮离子转运的效应，研究通过检测短路电流（short-circuit current，Isc）开展分析；采用细胞内钙离子成像技术，观察原代培养小鼠气管上皮细胞中STS诱导的细胞内钙离子浓度（[Ca²+]i）变化。结果显示，在小鼠气管顶侧给予STS可引起短路电流升高，该效应可被毒蕈碱型乙酰胆碱受体（muscarinic acetylcholine receptor，mAChR）拮抗剂阿托品阻断。移除环境中的Cl⁻或应用钙离子激活氯离子通道（Ca2+-activated Cl− channel，CaCC）阻滞剂后，STS诱导的短路电流反应受到抑制。此外，STS可升高小鼠气管上皮细胞内的[Ca²+]i。综上，STS可通过依赖毒蕈碱型乙酰胆碱受体的途径，经钙离子激活氯离子通道刺激小鼠气管上皮的氯离子分泌。鉴于氯离子分泌在气道水化过程中的关键作用，本研究结果提示，STS或可用于改善囊性纤维化（cystic fibrosis，CF）与慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）患者的气道脱水症状。