Sodium tanshinone IIA sulfonate stimulated Cl- secretion in mouse trachea.
Sodium tanshinone IIA sulfonate stimulated Cl- secretion in mouse trachea.
复制标题
丹参酮IIA磺酸钠刺激小鼠气管Cl-分泌
DOI：
10.1371/journal.pone.0178226
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zhou WL
中科院分区：
文献类型：
--
作者：
Chen PX;Zhang YL;Xu JW;Yu MH;Huang JH;Zhao L;Zhou WL
丹参酮IIA磺酸钠（STS）是丹参酮IIA的衍生物，丹参酮IIA是丹参中的一种亲脂性化合物。本研究旨在探讨STS对小鼠气管上皮离子转运的影响及其机制。通过测量短路电流（Isc）来评价STS对上皮离子转运的影响。细胞内Ca2+成像观察STS诱导原代培养小鼠气管上皮细胞内Ca2+浓度（[Ca2+]i）的变化。结果表明，在小鼠气管顶端应用STS可引起Isc升高，而这一作用被毒蕈碱乙酰胆碱受体（mAChR）拮抗剂阿托品消除。通过去除环境Cl -或使用Ca2+激活的Cl -通道（CaCC）阻滞剂，sts诱导的Isc反应被抑制。此外，STS升高了小鼠气管上皮细胞中的[Ca2+]i。结果表明，STS通过CaCC以一种依赖于machr的方式刺激小鼠气管上皮中Cl -的分泌。由于Cl−分泌在气道水化中的关键作用，我们的研究结果表明，STS可能用于改善囊性纤维化（CF）和慢性阻塞性肺疾病（COPD）的气道脱水症状。
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).