Yu Pengcheng, Lu Weiqi, Sun Huaxin, Huang Chengchen, Zhou Xiaolin, Wang Yuxing, Zhang Zhen, Fu Guosheng, Liu Hanxiong, Ren Kefeng, Sheng Xia
Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Engineering Research Center for Cardiovascular Innovative Devices of Zhejiang Province, Hangzhou 310016, China.
Regen Biomater. 2025 May 14;12:rbaf040. doi: 10.1093/rb/rbaf040. eCollection 2025.
Postoperative atrial fibrillation (POAF) is the most prevalent form of secondary atrial fibrillation and increases the risk of adverse cardiovascular outcomes, such as stroke, heart failure and increased mortality. Herein, we designed an andrographolide (Andr)-loaded degradable polymer patch to deliver the drug directly to the atrial tissue for prevention of POAF. The sterile pericarditis (SP) rat model was adopted for highly relationship to clinical practice. The patch-released Andr effectively reduced the incidence of atrial fibrillation from 90 to 20%, and alleviated local atrial inflammation and oxidative stress , by using electrophysiological detection and histological analysis such as immunofluorescence, western blot and PCR. In HL-1 cells, we found the use of Andr-loaded patch could strongly inhibit the cell death, reactive oxygen species (ROS) generation and mitochondrial injury caused by LPS. Meanwhile, the use of Andr-loaded patch could effectively inhibited macrophages polarize towards M1. Mechanistically, we verified that the regulation of the cytoplasm and mitochondria Ca and ROS dynamic balance was quite important both and . Our strategy proved by regulating the inflammatory microenvironment, ROS balance and Ca homeostasis and the Andr-loaded atrial patch was effective for POAF in the SP rat model. The electrical signal of atrial stromal reentry in the case of this model was successfully mined, and the results of calcium channel were basically consistent with that of electrical signal channel. In addition, we have reported the infiltration and polarization of local inflammatory cells in the atrial of POAF at the tissue section level. Our study served as a new inspiration for the treatment of arrhythmic diseases and other ROS- and Ca- associated local illnesses.
术后心房颤动(POAF)是继发性心房颤动最常见的形式,会增加不良心血管结局的风险,如中风、心力衰竭和死亡率增加。在此,我们设计了一种负载穿心莲内酯(Andr)的可降解聚合物贴片,将药物直接递送至心房组织以预防POAF。采用无菌性心包炎(SP)大鼠模型,因为其与临床实践高度相关。通过电生理检测和免疫荧光、蛋白质印迹及聚合酶链反应等组织学分析发现,贴片释放的Andr可有效将心房颤动的发生率从90%降至20%,并减轻局部心房炎症和氧化应激。在HL-1细胞中,我们发现使用负载Andr的贴片可强烈抑制脂多糖引起的细胞死亡、活性氧(ROS)生成和线粒体损伤。同时,使用负载Andr的贴片可有效抑制巨噬细胞向M1极化。从机制上讲,我们证实细胞质和线粒体钙及ROS动态平衡的调节在两者中都非常重要。我们的策略通过调节炎症微环境、ROS平衡和钙稳态得到验证,负载Andr的心房贴片对SP大鼠模型中的POAF有效。成功挖掘了该模型情况下心房基质折返的电信号,钙通道结果与电信号通道结果基本一致。此外,我们在组织切片水平报道了POAF心房中局部炎症细胞的浸润和极化。我们的研究为心律失常疾病及其他与ROS和钙相关的局部疾病的治疗提供了新的思路。