布比卡因对人肺上皮细胞短路电流影响的研究  

Effects of bupivacaine on short-circuit currents in human alveolar epithelial cells

作　　者：崔湧[1] 姜学东[2] 于同[3] 丁炎[3] 聂宏光[3] 

机构地区：[1]中国医科大学附属第一医院麻醉科,辽宁沈阳110001 [2]武警辽宁省总队医院胸外科,辽宁沈阳110034 [3]中国医科大学代谢病分子机制与药物研究所,辽宁沈阳110122

出　　处：《中国药理学通报》2017年第2期197-200,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81270098);辽宁省自然科学基金资助项目(No2014021093)

摘　　要：目的布比卡因是长效酰胺类局麻药,本研究旨在观察布比卡因对人肺上皮细胞短路电流的影响,并探讨可能的机制。方法应用尤斯灌流室装置测定H441单层细胞的短路电流。由总电流减去阿米洛利抑制后的电流算得阿米洛利敏感性电流,以用药前H441单层细胞的阿米洛利敏感性电流初始值为100%对照。用100μmol·L^(-1)布比卡因处理H441细胞,在0、15、30、60 min 4个时间点提取蛋白用于Western blot,研究布比卡因对ERK1/2蛋白磷酸化的影响。结果布比卡因能够剂量依赖性抑制H441单层细胞的短路电流,此电流可被阿米洛利抑制;Western blot结果显示,布比卡因能够促进ERK1/2蛋白磷酸化。结论布比卡因通过抑制人肺上皮细胞阿米洛利敏感性电流而降低肺泡上皮离子转运,其机制可能与其促进ERK1/2蛋白磷酸化有关。临床上对伴有肺部疾患的病人应用布比卡因时应考虑其可能对肺泡上皮液体清除的影响。Aim Bupivacaine is a kind of long-acting amide local anesthetics.This paper aims to explore the effects of bupivacaine on the short-circuit currents in human alveolar epithelial monolayers and study the possible mechanisms.Methods Short-circuit currents were recorded by ussing-chamber setup.Amiloride-sensitive currents were defined as the difference be-tween the total current and the amiloride-resistant cur-rent.ERK1 /2 phosphorylation protein levels were ana-lyzed by Western blot at 0,1 5,30 and 60 min after administration of 1 00 μmol·L^-1 bupivacaine.Results Bupivacaine could inhibit the short-circuit currents in H441 monolayers dose-dependently,which could be inhibited by amiloride.Western blot analysis showed that bupivacaine increased the level of ERK1 /2 phos-phorylation.Conclusion These data demonstrate that bupivacaine can reduce the alveolar ion transport by in-hibiting the amiloride-sensitive currents,possibly by the enhancement of ERK1 /2 phosphorylation. The effects of alveolar fluid clearance following application of bupivacaine should be considered clinically when the patient is complicated with lung injury.

关 键 词：布比卡因 短路电流 上皮钠通道 蛋白磷酸化 肺水肿 肺泡液体清除率 

分 类 号：R322.35[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]