Ye Tianxin, Zhang Cui, Wu Gang, Wan Weiguo, Guo Yan, Fo Yuhong, Chen Xiuhuan, Liu Xin, Ran Qian, Liang Jinjun, Shi Shaobo, Yang Bo
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Cardiovascular Research Institute, Wuhan University, Wuhan, China.
Front Pharmacol. 2020 Nov 24;11:547966. doi: 10.3389/fphar.2020.547966. eCollection 2020.
Depression is associated with the increased risk of mortality and morbidity and is an independent risk factor for many cardiovascular diseases. Depression may promote cardiac arrhythmias, but little is known about the mechanisms. Pinocembrin mitigated depressive-like behaviors and exhibited cardioprotective effects in several models; however, whether pinocembrin benefits ventricular arrhythmias in depression models has not been elucidated. Thus, this study was to evaluate the effects of pinocembrin on ventricular fibrillation susceptibility in rat models of depression. Male Sprague-Dawley rats were randomly assigned into control, control + pinocembrin, MDD (major depressive disorder), and MDP (MDD + pinocembrin) groups, respectively. Depressive-like behaviors, ventricular electrophysiological parameters, electrocardiogram parameters, heart rate variability, ventricular histology, serum norepinephrine, tumor necrosis factor-α, and interleukin-1β were detected. Protein levels in left ventricle were measured by Western blot assays. Compared with the MDD group, pinocembrin significantly mitigated depressive-like behaviors, prolonged ventricular effective refractory period, action potential duration, QT, and corrected QT (QTc) interval, improved heart rate variability, decreased Tpeak-Tend interval, ventricular fibrillation inducibility rate, ventricular fibrosis, ventricular positive nerve densities, and protein expression of tyrosine hydroxylase and growth associated protein-43, reduced serum norepinephrine, tumor necrosis factor-α, interleukin-1β concentrations, and the expression levels of p-IκBα and p-p65, and increased the protein expression of Cx43, Cav1.2, and Kv.4.2 in the MDP group. Pinocembrin attenuates ventricular electrical remodeling, autonomic remodeling, and ion-channel remodeling, lowers ventricular fibrosis, and suppresses depression-induced inflammatory responses, providing new insights in pinocembrin and ventricular arrhythmias in depressed patients.
抑郁症与死亡率和发病率的增加相关，并且是许多心血管疾病的独立危险因素。抑郁症可能会促发心律失常，但其机制尚不清楚。白杨素在多种模型中减轻了抑郁样行为并表现出心脏保护作用；然而，白杨素对抑郁症模型中的室性心律失常是否有益尚未阐明。因此，本研究旨在评估白杨素对抑郁症大鼠模型心室颤动易感性的影响。雄性Sprague-Dawley大鼠被随机分为对照组、对照+白杨素组、重度抑郁症（MDD）组和MDD+白杨素（MDP）组。检测抑郁样行为、心室电生理参数、心电图参数、心率变异性、心室组织学、血清去甲肾上腺素、肿瘤坏死因子-α和白细胞介素-1β。通过蛋白质免疫印迹法检测左心室中的蛋白质水平。与MDD组相比，白杨素显著减轻了抑郁样行为，延长了心室有效不应期、动作电位时程、QT和校正QT（QTc）间期，改善了心率变异性，缩短了T波峰-末间期、心室颤动诱发率、心室纤维化、心室阳性神经密度以及酪氨酸羟化酶和生长相关蛋白-43的蛋白表达，降低了血清去甲肾上腺素、肿瘤坏死因子-α、白细胞介素-1β浓度以及p-IκBα和p-p65的表达水平，并增加了MDP组中Cx43、Cav1.2和Kv.4.2的蛋白表达。白杨素减轻了心室电重构、自主神经重构和离子通道重构，降低了心室纤维化，并抑制了抑郁症诱导的炎症反应，为白杨素和抑郁症患者的室性心律失常提供了新的见解。
