Na^+/K^+ATPase介导甘草诱导低钾血症的研究  

Molecular mechanism and treatment of hypokalemia induced by high dose of Glycyrrhiza uralensis decoction

作　　者：张亚倩 徐鹏程[1] 张琴 徐榕 张文峰[1] 沈晗[1] 陶嫦立 邵红伟[1] ZHANG Yaqian;XU Pengcheng;ZHANG Qin;XU Rong;ZHANG Wenfeng;SHEN Han;TAO Changli;SHAO Hongwei(School of Biosciences and Biopharmaceutics,Guangdong Pharmaceutical University,Guangdong Key Laboratory of Biotechnology Candidate Drug Research,Guangzhou 510006,China)

机构地区：[1]广东药科大学生命科学与物物制药学院广东省生物技术候选药物研究重点实验室,广东广州510006

出　　处：《广东药科大学学报》2019年第2期268-273,共6页Journal of Guangdong Pharmaceutical University

基　　金：国家自然科学基金项目(31100664;31300737;31400149);广东省自然科学基金项目(2014A030313586);广东省科技计划项目(2016A020215157);广东省高等教育"创新强校工程"项目(2017KZDXM049;2017KCXTD020)

摘　　要：目的探讨高剂量甘草水提物导致小鼠低钾血症的分子机制。方法利用高剂量甘草水提物(7.5 g/kg)灌胃制备低钾血症小鼠模型,收集小鼠尿液和粪便,检测其K^+浓度;分析小鼠肠道组织的转录组数据,寻找与钾代谢相关基因的表达变化,并利用real-time PCR进行确认;针对显著改变的关键基因进行干预,确认其与甘草诱导低钾血症的关系。结果高剂量甘草水提物可造成小鼠低钾血症,转录组结果表明Na^+/K^+ATPase的表达水平发生显著变化,real-time PCR结果也确证了这一点,肠道病理切片显示肠道通透性发生改变;低钾血症小鼠的尿钾降低,而粪便中K^+浓度增多,表明甘草水提物诱导的低钾血症可能主要由肠道失钾造成;给予Na^+/K^+ATPase抑制剂处理后,尿液中K^+浓度快速升高,粪便中的K^+浓度降低;继续予以高剂量甘草水提物处理,在Na^+/K^+ATPase抑制剂药效消除后小鼠尿液和粪便中K^+浓度又恢复至造模状态。结论高剂量甘草水提物造成的低钾血症主要是由胃肠道失钾造成的,而这种低钾血症可以通过Na^+/K^+ATPase抑制剂特异性地进行逆转。Objective To explore the molecular mechanism of hypokalemia induced by high dose of Glycyrrhiza uralensis decoction in mice.Methods Hypokalemia mice model was established by gavage administration of high dose of Glycyrrhiza uralensis decoction (7.5 g/kg).K^+ concentration in urine and feces of mice was detected.The transcriptome data of intestinal tissues of mice were analyzed to find out the expression changes of genes related to potassium metabolism and altered expression was further confirmed by real-time PCR.The pathological sections of the intestine were observed to reveal the changes of intestinal permeability.The key gene with altered expression was selected as intervention target to confirm its relationship with Glycyrrhiza-induced hypokalemia.Results High dose of Glycyrrhiza uralensis decoction caused hypokalemia in mice.Transcriptome data showed that the expression level of Na^+/K^+ ATPase changed significantly,which was confirmed by real-time PCR.The decreased urinary potassium and the increased K^+ concentration in feces in hypokalemia mice indicated that the hypokalemia induced by Glycyrrhiza uralensis decoction may be mainly caused by intestinal potassium loss.After treatment with Na^+/K^+ ATPase inhibitor,K^+ concentration in urine increased rapidly and K^+ concentration in feces decreased.Continued treatment with high dose of Glycyrrhiza uralensis decoction,K^+ concentration in urine and feces of mice reversed when elimination of Na^+/K^+ ATPase inhibitor.Conclusion Hypokalemia induced by high dose of Glycyrrhiza aqueous extract is mainly caused by gastrointestinal potassium loss,which can be specifically abrogated by Na^+/K^+ ATPase inhibitors.

关 键 词：甘草 低钾血症 Na^+/K^+ATPase抑制剂 

分 类 号：R966[医药卫生—药理学]