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藿香正气水对猪远端气道完整上皮HCO_(3)~(-)分泌的作用

谢晨, 王晓飞, 祁秀娟, 卢丽丽, 陈小章

香港中文大学医学院生理学系上皮细胞生物学研究中心.香港；中国海洋大学海洋生命学院.山东,青岛 266003；青岛大学医学院附属医院.山东,青岛 266003

摘要

该文应用短路电流技术检测了cAMP激动剂forskolin／IBMX和中成药藿香正气水（Huoxiang--zhengqi liquid，HZL）对猪远端气道完整上皮HCO_(3)~(-)分泌的作用。新鲜分离的气道上皮组织可测得（94.9±8.2）#mu#A/cm~(2)的跨上皮基础电流，其中的16,6％和62,7％可分别被amiloride（上皮钠离子通道阻断剂，100#mu#mol／L）和NPPB（囊性纤维化跨膜电导调节体Cl~(-)通道阻断剂，100#mu#mol／L）所阻断。用葡萄糖酸根替代浴液中的Cl~(-)，跨上皮基础电流降低为（54.0±6.7）#mu#A／cm~(2)，当进一步替代掉浴液中HCO_(3)~(-)时，此电流可被去除，提示在未受刺激条件下存在HCO_(3)~(-)分泌。forskolin／IBMX可刺激HCO_(3)~(-)依赖的电流增加（7.3±0.5）#mu#A/cm~(2)。值得注意的是，HZL也能引起HCO_(3)~(-)电流增加（7.4±1.9）#mu#A／cm~(2)，而这种刺激作用不受forskolin／IBMX预处理的影响，提示一种不依赖于cAMP的信号通路。以上结果提示，无论是否受刺激，猪远端气道上皮都分泌HCO_(3)~(-)。HZL对远端气道上皮HCO_(3)~(-)分泌的刺激作用，提示其有希望成为一种新的、有治疗意义的远端气道HCO_(3)~(-)分泌刺激剂。

关键词： 离子转运; 碳酸氢根; 囊性纤维化跨膜电导调节体; 气道

Effect of Huoxiang--zhengqi liquid on HCO_(3)~(-) secretion by intact porcine distal airway epithelium

Xie Chen, Wang Xiaofei, Qi Xiujuan, Lu Lili, Chen Xiaozhang

Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong.Hong Kong；China；The Affiliated Hospital of Medical College of Qingdao University.Qingdao 266003,Shandong

Abstract

The short-circuit current （I_(SC)） technique was used to examine the effects of cAMP-evoking agents, forskolin/IBMX, and a Chinese medicinal formula, Huoxiang-zhengqi liquid （HZL） on HCO_(3)~(-) secretion by intact porcine distal airway epithelium. The freshly isolated airway epithelial tissue displayed a transepithelial basal current of （94.9±8.2）#mu#A/cm~(2), 16.6% and 62.7% of which was inhibited by amiloride （epithelial Na~(+) channel blocker, 100 #mu#mol/L） and NPPB （cystic fibrosis transmembrane conductance regulator Cl~(-) channel blocker, 100 #mu#mol/L）. Substitution of Cl~(-) with impermeable gluconate~(-) in the K-H bath solution resulted in a basal current of （54.0±6.7）#mu#A/cm~(2), which could be abolished by further removal of HCO_(3)~(-) in the solution, indicating HCO_(3)~(-) secretion under unstimulated conditions. Application of forskolin/IBMX （10 #mu#mol/L/100 #mu#mol/L） stimulated an increase of （13.8±1.9）#mu#A/cm~(2) in I_(SC) which could be blocked by Cl~(-) channel inhibitor DPC. With Cl~(-) and Cl~(-)/HCO_(3)~(-) substitution, forskolin/IBMX evoked an increase of （7.3±0.5） #mu#A/cm~(2) in HCO_(3)~(-)-dependent, DPC-inhibitable I_(SC) （I_(HCO_(3))）. Noticeably, basolateral application of HZL （10#mu#L/mL） in normal K-H solution evoked an I_(SC) of （15.9±2.4）#mu#A/cm~(2). The EC_(50) of this I_(SC) was （6.1±1.4） #mu#L/mL. When substituting Cl~(-), HZL stimulated an increase of （7.4±1.9）#mu#A/cm~(2) in I_(HCO_(3)), suggesting HZL-induced I_(HCO_(3)) secretion. After pretreating the epithelial tissues with forskolin/IBMX in Cl~(-)-free K-H solution, HZL induced a further increase of （8.4±0.9）#mu#A/cm~(2) in I_(HCO_(3)), and pretreating tissues with HZL did not significantly affect the subsequent forskolin/IBMX-induced I_(HCO_(3)) response, indicating that HZL- and forskolin/IBMX-induced I_(HCO_(3)) responses appeared to be independent and be most likely mediated via different cellular mechanisms. Our results suggest that HCO_(3)~(-) can be secreted by porcine distal airway epithelium under unstimulated and stimulated conditions, and the stimulatory effect of HZL on HCO_(3)~(-) secretion in the distal airway epithelium shows HZL to be a hopeful new agonist for distal airway HCO_(3)~(-) secretion that could be of therapeutic significance.

Key words: ion transport;bicarbonate;cystic fibrosis transmembrane conductance regulator;airway

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引用本文：

谢晨, 王晓飞, 祁秀娟, 卢丽丽, 陈小章. 藿香正气水对猪远端气道完整上皮HCO_(3)~(-)分泌的作用[J]. 生理学报 2008; 60 (1): 90-96.

Xie Chen, Wang Xiaofei, Qi Xiujuan, Lu Lili, Chen Xiaozhang. Effect of Huoxiang--zhengqi liquid on HCO_(3)~(-) secretion by intact porcine distal airway epithelium. Acta Physiol Sin 2008; 60 (1): 90-96 (in Chinese with English abstract).