川陈皮素对囊性纤维化跨膜传导调节因子的激活作用
he activation effect of nobiletin on cystic fibrosis transmenbrance conductance regulator chloride channel
目的：研究川陈皮素（nobiletin）对囊性纤维化跨膜传导因子（cystic fibrosis transmembrane conductance regulator, CFTR）氯离子通道的激活作用。方法：利用荧光淬灭实验和膜片钳技术在稳定表达人CFTR和荧光绿蛋白突变体EYFP/H148Q的Fischer大鼠甲状腺上皮细胞（Fischer rat thyroid, FRT）上，测定川陈皮素对CFTR Cl－通道活性的影响。结果：发现川陈皮素以剂量依赖的方式激活CFTR氯离子通道的Cl－转运活性，且这种活性是快速、可逆的，并能够被CFTR特异性抑制剂CFTRinh-172完全抑制。初步的分子机制研究表明川陈皮素是以与CFTR直接作用来激活通道活性的。进一步的研究结果显示，川陈皮素能够有效地刺激小鼠气管粘膜下腺液体分泌速度。因此，川陈皮素可能发展成为治疗包括支气管扩张在内的CFTR相关疾病的先导药物。
im: Aim of the present study is to investigate activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator（CFTR）chloride channel activity. Method: CFTR-mediated iodide influx assay and patch-clamp tests were done on FRT cells stably co-transfected with human CFTR and EYFP/H148Q. Result: Nobiletin potently activated CFTR chaloride channel activity in a dose- and time-dependent manner. The CFTR blocker CFTRinh-172 could completely reverse the effect. Primary mechanism study indicated that nobiletin activated CFTR chloride channel through a direct binding way. In addition, ex vivo tests done on mice trachea showed that nobiletin time-dependently stimulated submucosal gland fluid secretion. Nobiletin may present a therapeutic lead compound in treating CFTR-related diseases including disseminated bronchiectasis.
张耀方、王雪、杨爽、杨红、于波
基础医学药学生理学
细胞生物学囊性纤维化跨膜传导因子川陈皮素激活剂
cell biologyCFTRnobiletinactivator
张耀方,王雪,杨爽,杨红,于波.川陈皮素对囊性纤维化跨膜传导调节因子的激活作用[EB/OL].(2012-12-14)[2025-08-16].http://www.paper.edu.cn/releasepaper/content/201212-313.点此复制
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