Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 1):33-40. doi: 10.1016/j.bbrc.2022.10.036. Epub 2022 Oct 22.
Inflammation can contribute to the initiation and progression of atrial fibrillation (AF), and pinocembrin can suppress downstream inflammatory cytokine production by inhibiting the inflammation pathway. In our previous studies, pinocembrin was also beneficial in ameliorating cardiac arrhythmia in different models of rats, such as depression, myocardial infarction, and heart failure. This study aims to investigate the effect of pinocembrin on the susceptibility to AF in isoproterenol-induced rats.
Rats were randomly divided into four groups. Pinocembrin was injected through the tail vein. Isoproterenol was treated by intraperitoneal injection for one week (5 mg/kg/day). We evaluated the susceptibility to AF by atrial electrophysiological experiments. Masson staining was used to evaluate the fibrosis area. The protein levels of connexin (Cx) 40, Cav1.2, Kv4.2, collagen I, collagen III, α-SMA, transforming growth factor (TGF)-β, NLRP3, caspase 1, and interleukin (IL)-1β were detected by western blot.
Our data demonstrated that pinocembrin could prolong the atrial effective refractory period (ERP) and action potential duration (APD), and decrease AF inducibility. Isoproterenol increased the expression of Cav1.2 and Kv4.2 ion channels whereas pinocembrin could alleviate this change. Pinocembrin could reduce the fibrosis area, fibrosis-related protein collagen I, collagen III, α-SMA, and TGF-β and upregulate gap junction protein Cx40. In addition, pinocembrin reduced the expression of NLRP3, caspase 1, and IL-1β.
Our study indicated that pinocembrin was beneficial to alleviate atrial electrical remodeling and fibrosis. Accompanied the downregulation of ion channels and upregulation of gap junction protein Cx40. Pinocembrin may produce these effects by inhibiting the NLRP3 pathway.
炎症可导致心房颤动（AF）的发生和发展，而白杨素可通过抑制炎症途径抑制下游炎性细胞因子的产生。在我们之前的研究中，白杨素对改善不同大鼠模型中的心律失常也有好处，如抑郁、心肌梗死和心力衰竭。本研究旨在探讨白杨素对异丙肾上腺素诱导的大鼠 AF 易感性的影响。
大鼠随机分为四组。白杨素经尾静脉注射。异丙肾上腺素通过腹腔注射处理一周（5mg/kg/天）。我们通过心房电生理实验评估 AF 的易感性。Masson 染色用于评估纤维化面积。通过 Western blot 检测连接蛋白（Cx）40、Cav1.2、Kv4.2、胶原 I、胶原 III、α-SMA、转化生长因子（TGF）-β、NLRP3、半胱天冬酶 1 和白细胞介素（IL）-1β的蛋白水平。
我们的数据表明，白杨素可以延长心房有效不应期（ERP）和动作电位时程（APD），并降低 AF 的诱导性。异丙肾上腺素增加 Cav1.2 和 Kv4.2 离子通道的表达，而白杨素可以减轻这种变化。白杨素可以减少纤维化面积、纤维化相关蛋白胶原 I、胶原 III、α-SMA 和 TGF-β，上调间隙连接蛋白 Cx40。此外，白杨素降低了 NLRP3、半胱天冬酶 1 和 IL-1β的表达。
我们的研究表明，白杨素有利于缓解心房电重构和纤维化。伴随着离子通道的下调和间隙连接蛋白 Cx40 的上调。白杨素可能通过抑制 NLRP3 途径产生这些作用。
