Cardiotonic actions of quercetin and its metabolite tamarixetin through a digitalis-like enhancement of Ca 2+ transients
Cardiotonic actions of quercetin and its metabolite tamarixetin through a digitalis-like enhancement of Ca 2+ transients
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槲皮素及其代谢物 Tamarixetin 通过洋地黄样增强 Ca 2 瞬变的强心作用
DOI：
10.1016/j.abb.2017.11.009
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发表时间：
2018
影响因子：
3.9
通讯作者：
Sasaguri Toshiyuki
中科院分区：
文献类型：
--
作者：
Hayamizu Kengo;Morimoto Sachio;Nonaka Miki;Hoka Sumio;Sasaguri Toshiyuki
槲皮素（QCT）是一种植物源性黄酮类化合物，具有多种生物学作用，包括抗氧化和抗炎作用引起的心脏保护作用。在这项研究中，QCT及其代谢产物对小鼠单个心肌细胞的收缩和钙瞬变（Ca 2 + transients，CaT）的影响，同时测量和比较异丙肾上腺素和地高辛。此外，在小鼠中静脉推注QCT后分析心脏功能和血浆浓度。QCT及其代谢产物tamarixlavin，以及异丙肾上腺素和地高辛，增强心肌细胞的收缩和CaT。异丙肾上腺素的变力作用伴随着肌节缩短和再延长的速度增加以及通过激活cAMP依赖性蛋白激酶引起的CaT衰减;然而，QCT、tamarixaline或地高辛的变力作用没有这种增力作用。小鼠静脉注射QCT导致心脏收缩功能持续增加; QCT快速代谢为tamarixlavin，其血浆浓度在与心脏收缩功能增强相似的时间范围内维持在高水平。这些结果表明，QCT在体内发挥强心作用，至少，部分地，通过洋地黄样增强钙本身及其代谢产物tamarixalloy。
The plant-derived flavonoid, quercetin (QCT), has many biological actions, including cardioprotective actions, resulting from its antioxidant and anti-inflammatory effects. In this study, effects of QCT and its metabolites on the contraction and Ca2+ transients (CaT) of mouse single cardiomyocytes were simultaneously measured and compared with those of isoproterenol and digoxin. Furthermore, cardiac function and plasma concentrations were analyzed after bolus intravenous administration of QCT in mice. QCT and its metabolite, tamarixetin, as well as isoproterenol and digoxin, enhanced the contraction and CaT of cardiomyocytes. The inotropic action of isoproterenol was accompanied by an increase in the velocities of sarcomere shortening and relengthening and CaT decay through activation of cAMP-dependent protein kinase; however, no such lusitropic effects accompanied the inotropic action of QCT, tamarixetin or digoxin. Intravenous administration of QCT to mice resulted in a sustained increase in cardiac systolic function; QCT was rapidly metabolized to tamarixetin and its plasma concentration was maintained at high levels over a similar time frame as the enhancement of cardiac systolic function. These results suggest that QCT exerts a cardiotonic action in vivo at least, in part, through digitalis-like enhancement of CaT by itself and its metabolite tamarixetin.