Zhang Bo, Cui Xun, Jin Hong-Hua, Hong Lan, Liu Xia, Li Xiang, Zhang Qing-Gao, Liu Li-Ping
Department of Physiology and Pathophysiology, School of Medicine, Yanbian University, Yanji 133002, China.
Department of Physiology and Pathophysiology, School of Medicine, Yanbian University, Yanji 133002, China; Key Laboratory of Organism Functional Factors of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China; Cellular Function Research Center, Yanbian University, Yanji 133002, China.
Life Sci. 2017 Dec 1;190:36-45. doi: 10.1016/j.lfs.2017.09.027. Epub 2017 Sep 27.
Ginsenoside Re (G-Re), a major ginsenoside in ginseng, has many beneficial pharmacological effects on negative cardiac contractility, electromechanical alternans, antiarrhythmia, angiogenic regeneration and cardiac electrophysiological function. However, effects of G-Re on gap-junction remodeling are unclear. Therefore, this study aimed to investigate the effect of G-Re on angiotensin II (Ang II)-induced downregulation of connexin-40 (CX40) and -43 (CX43) in beating rat left atria.
In this study, the isolated perfused beating rat atrial model was used and atrial gap-junction remodeling was induced by Ang II. In vivo hemodynamic experiments were analyzed with a biological recorder. Changes in protein expression were analyzed by western blot.
G-Re attenuated Ang II-induced abnormal changes in heart rate, MAP, LVESP, LVEDP, +dp/dt max, -dp/dt min, P wave amplitude, P-R interval and P wave length. This indicated a dose-dependent preventive role against Ang II-induced hyper hemodynamics in rats. Atrial activities of p38 mitogen-activated protein kinase (MAPK), nuclear factor kappa-B (NF-κB) and activator protein 1 (AP-1) were significantly increased by Ang II, as was expression of atrial collagen I and matrix metalloproteinase 2 (MMP2). Atrial CX40 and CX43 expression was downregulated by Ang II. These Ang II-induced atrial effects were blocked by G-Re, as well as rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ (PPARγ), in a dose-dependent manner. However, this inhibition was abolished by the PPARγ inhibitor GW9662.
G-Re may suppress Ang II-induced downregulation of CX40 and CX43, by activating PPARγ signaling, in isolated perfused beating rat atria.
人参皂苷Re（G-Re）是人参中的一种主要人参皂苷，对负性心脏收缩力、电机械交替、抗心律失常、血管生成性再生及心脏电生理功能具有多种有益的药理作用。然而，G-Re对缝隙连接重塑的影响尚不清楚。因此，本研究旨在探讨G-Re对血管紧张素II（Ang II）诱导的搏动大鼠左心房中连接蛋白40（CX40）和连接蛋白43（CX43）下调的影响。
本研究采用离体灌注搏动大鼠心房模型，并用Ang II诱导心房缝隙连接重塑。用生物记录仪分析体内血流动力学实验。通过蛋白质免疫印迹法分析蛋白质表达的变化。
G-Re减轻了Ang II诱导的心率、平均动脉压、左心室收缩末期压、左心室舒张末期压、最大上升速率、最大下降速率、P波振幅、P-R间期和P波长度的异常变化。这表明其对Ang II诱导的大鼠高血流动力学具有剂量依赖性的预防作用。Ang II可显著增加p38丝裂原活化蛋白激酶（MAPK）、核因子κB（NF-κB）和活化蛋白1（AP-1）的心房活性，以及心房I型胶原蛋白和基质金属蛋白酶2（MMP2）的表达。Ang II可下调心房CX40和CX43的表达。G-Re以及过氧化物酶体增殖物激活受体γ（PPARγ）激动剂罗格列酮可剂量依赖性地阻断这些Ang II诱导的心房效应。然而，PPARγ抑制剂GW9662可消除这种抑制作用。
在离体灌注搏动大鼠心房中，G-Re可能通过激活PPARγ信号通路抑制Ang II诱导的CX40和CX43下调。
