Kimoto A, Hirano Y, Iwai T, Saitou M, Tomioka K, Miyata K, Yamada T
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan.
Biol Pharm Bull. 2000 Dec;23(12):1441-4. doi: 10.1248/bpb.23.1441.
The effects of the surfactant secretagogue YM-40461 on the mucociliary transport (MCT) velocity were examined in guinea pigs with induced bronchitis. Guinea pigs were exposed to SO2 gas (900 ppm, 3 h/d) for 5 d. MCT velocity was measured by the movement of a 30% gelatin solution containing Evans blue dye placed on the tracheal mucosal surface. Repeated doses of YM-40461 improved the MCT guinea pigs with bronchitis within 5 d after the completion of SO2 exposure, with an ED50 value of 3.1 mg/kg p.o. At a dose of 10 mg/kg p.o., YM-40461 restored MCT to the control level (98.0% recovery). Ambroxol, bromhexine and salbutamol also improved MCT, but were far less effective than YM-40461. Airway fluid collected from bronchitic animals revealed increased disaturated phosphatidylcholine (DSPC, a major component of surfactants)-to-protein ratio and decreased surface tension produced by YM-40461 treatment (10 mg/kg). These results suggest that YM-40461 ameliorates MCT dysfunction in animals with SO2 gas-induced bronchitis by increasing the DSPC-to-protein ratio in the airway.
在诱导性支气管炎豚鼠中研究了表面活性剂促分泌剂YM-40461对黏液纤毛运输（MCT）速度的影响。将豚鼠暴露于二氧化硫气体（900 ppm，每天3小时）中5天。通过放置在气管黏膜表面的含伊文思蓝染料的30%明胶溶液的移动来测量MCT速度。在二氧化硫暴露结束后的5天内，重复给予YM-40461可改善患支气管炎豚鼠的MCT，口服的半数有效剂量（ED50）值为3.1 mg/kg。口服剂量为10 mg/kg时，YM-40461可使MCT恢复至对照水平（恢复率98.0%）。氨溴索、溴己新和沙丁胺醇也可改善MCT，但效果远不如YM-40461。从患支气管炎动物收集的气道液体显示，经YM-40461（10 mg/kg）处理后，二饱和磷脂酰胆碱（DSPC，表面活性剂的主要成分）与蛋白质的比例增加，表面张力降低。这些结果表明，YM-40461通过增加气道中DSPC与蛋白质的比例来改善二氧化硫气体诱导的支气管炎动物的MCT功能障碍。
