State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, Liaoning 110016, PR China; Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, PR China.
State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, Liaoning 110016, PR China.
Int Immunopharmacol. 2024 Dec 5;142(Pt B):113196. doi: 10.1016/j.intimp.2024.113196. Epub 2024 Sep 21.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinic, and type 2 diabetes mellitus (T2DM) is an independent risk factor for AF. Salidroside (Sal), the active ingredient of the Rhodiola rosea, has hypoglycemic, anti-inflammatory, anti-fibrotic and anti-arrhythmic effects. The aim of this study is to investigate the effects and underlying molecular mechanisms of Sal on T2DM associated atrial inflammation and the pathogenesis of AF. In the in vivo study, T2DM mice model was established by high-fat diet and intraperitoneal injection of streptozotocin (STZ). Sal (25 mg/kg/d, 50 mg/kg/d, and 100 mg/kg/d) was administered orally for 4 weeks. T2DM caused atrial electrical and structural remodeling and significantly increased the susceptibility of AF. Meanwhile, mTOR-STAT3-MCP-1 signaling and inflammatory markers were also significantly enhanced in diabetic atria. However, Sal dose-dependently ameliorated cardiac dysfunction, mitigated atrial structural and electrical remodeling, and reduced atrial inflammation. Moreover, Sal-treated group exhibited remarkably down-regulated activity of mTOR-STAT3-MCP-1 pathway, and decreased atrial monocyte/macrophage infiltration. In palmitic acid (PA)-challenged HL-1 cells, Sal attenuated cytotoxicity, downregulated the expressions of TNF-α, IL-6, MCP-1, and inhibited the activation of mTOR-STAT3 signaling. However, co-treatment with MHY1485 (a mTOR agonist) reversed these effects. Taken together, the present study demonstrates that Sal treatment decreases the susceptibility of AF in diabetic mice by reducing mTOR-STAT3-MCP-1 signaling and atrial monocyte/macrophage infiltration. Sal treatment may represent a novel preventive therapy for cardiac arrhythmia and atrial fibrillation in diabetic patients.
心房颤动（AF）是临床上最常见的持续性心律失常，2 型糖尿病（T2DM）是 AF 的独立危险因素。红景天苷（Sal）是红景天的活性成分，具有降血糖、抗炎、抗纤维化和抗心律失常作用。本研究旨在探讨 Sal 对 T2DM 相关心房炎症及 AF 发病机制的影响及潜在分子机制。在体内研究中，通过高脂肪饮食和腹腔注射链脲佐菌素（STZ）建立 T2DM 小鼠模型。Sal（25mg/kg/d、50mg/kg/d 和 100mg/kg/d）口服给药 4 周。T2DM 导致心房电重构和结构重构，并显著增加 AF 的易感性。同时，糖尿病心房中 mTOR-STAT3-MCP-1 信号和炎症标志物也显著增强。然而，Sal 呈剂量依赖性改善心脏功能障碍，减轻心房结构和电重构，并减少心房炎症。此外，Sal 处理组显示出显著下调 mTOR-STAT3-MCP-1 通路的活性，并减少心房单核细胞/巨噬细胞浸润。在棕榈酸（PA）刺激的 HL-1 细胞中，Sal 减轻细胞毒性，下调 TNF-α、IL-6、MCP-1 的表达，并抑制 mTOR-STAT3 信号的激活。然而，用 MHY1485（mTOR 激动剂）共同处理可逆转这些作用。综上所述，本研究表明，Sal 治疗通过减少 mTOR-STAT3-MCP-1 信号和心房单核细胞/巨噬细胞浸润，降低糖尿病小鼠 AF 的易感性。Sal 治疗可能为糖尿病患者的心律失常和心房颤动提供一种新的预防治疗方法。
