Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
J Ethnopharmacol. 2023 Nov 15;316:116742. doi: 10.1016/j.jep.2023.116742. Epub 2023 Jun 7.
Shexiang Tongxin Dropping Pill (STDP), a traditional Chinese medicine compound, is fragrant, invigorates the qi, unblocks pulses, activates the blood circulation, removes blood stasis, and relieves pain. It is used clinically to treat coronary heart disease and angina pectoris. Coronary microvascular dysfunction (CMD) is associated with increased morbidity and mortality from cardiovascular events. Endothelial dysfunction and inflammation have been verified as its underlying causes. STDP can ameliorate CMD, but the mechanism has not been fully elucidated.
To explore the effects of STDP on M1 macrophage polarization-induced inflammation and endothelial dysfunction as an inhibitor of CMD, and to determine its mechanisms of action.
The CMD rat model was established by left anterior descending artery (LAD) ligation. The efficacy of STDP against CMD was evaluated by echocardiography, optical microangiography, Evans blue staining, and histological examination. The OGD/R-induced endothelial injury model, the endothelial injury-induced sterile inflammation model, the Dectin-1 overexpression model, and the Dectin-1-overexpressing RAW264.7 macrophage supernatant-stimulated HUVEC-induced secondary injury of endothelial function model were established to confirm the efficacy of STDP against M1 macrophage polarization-induced inflammation and endothelial dysfunction.
STDP blunted the deterioration of cardiac function and ameliorated CMD by reducing inflammatory cell infiltration and endothelial dysfunction in CMD rats. Endothelial injury and Dectin-1 overexpression induced M1 macrophage polarization and inflammation. Mechanically, STDP hindered M1 macrophage polarization and inflammation by inhibiting the Dectin-1/Syk/IRF5 pathway both in vivo and in vitro. STDP alleviated endothelial dysfunction induced by Dectin-1 overexpression in macrophages.
STDP can alleviate M1 macrophage polarization-induced inflammation and endothelial dysfunction against CMD via the Dectin-1/Syk/IRF5 pathway. Dectin-1-associated M1 macrophage polarization might be developed as a novel target for ameliorating CMD.
麝香通心滴丸（STDP）是一种中药复方，具有芳香、益气、通脉、活血、化瘀、止痛的功效。临床上用于治疗冠心病、心绞痛。冠状动脉微血管功能障碍（CMD）与心血管事件的发病率和死亡率增加有关。内皮功能障碍和炎症已被证实是其潜在原因。STDP 可改善 CMD，但机制尚未完全阐明。
探讨 STDP 对 M1 巨噬细胞极化诱导的炎症和内皮功能障碍的作用，及其作为 CMD 抑制剂的作用机制。
通过左前降支（LAD）结扎建立 CMD 大鼠模型。通过超声心动图、光学微血管造影、伊文思蓝染色和组织学检查评估 STDP 对 CMD 的疗效。建立 OGD/R 诱导的内皮损伤模型、内皮损伤诱导的无菌性炎症模型、Dectin-1 过表达模型和 Dectin-1 过表达 RAW264.7 巨噬细胞上清液刺激 HUVEC 诱导内皮功能二次损伤模型，以确认 STDP 对 M1 巨噬细胞极化诱导的炎症和内皮功能障碍的疗效。
STDP 通过减少炎症细胞浸润和内皮功能障碍改善 CMD 大鼠心脏功能恶化。内皮损伤和 Dectin-1 过表达诱导 M1 巨噬细胞极化和炎症。在体内和体外，STDP 通过抑制 Dectin-1/Syk/IRF5 通路抑制 M1 巨噬细胞极化和炎症。STDP 减轻了 Dectin-1 过表达诱导的巨噬细胞内皮功能障碍。
STDP 通过 Dectin-1/Syk/IRF5 通路减轻 M1 巨噬细胞极化诱导的炎症和内皮功能障碍，改善 CMD。Dectin-1 相关的 M1 巨噬细胞极化可能成为改善 CMD 的新靶点。
