National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
BMC Complement Med Ther. 2023 Aug 18;23(1):289. doi: 10.1186/s12906-023-04112-7.
Panax quinquefolius saponin (PQS) was shown beneficial against platelet adhesion and for gastroprotection. This study aimed to investigate the integrated efficacy of PQS with dual antiplatelet therapy (DAPT) on platelet aggregation, myocardial infarction (MI) expansion and gastric injury in a rat model of acute MI (AMI) and to explore the mechanism regarding arachidonic acid (AA)-derived eicosanoids metabolism.
Wistar rats were subjected to left coronary artery occlusion to induce AMI model followed by treatment with DAPT, PQS or the combined therapy. Platelet aggregation was measured by light transmission aggregometry. Infarct size, myocardial histopathology was evaluated by TTC and H&E staining, respectively. Gastric mucosal injury was examined by scanning electron microscope (SEM). A comprehensive eicosanoids profile in plasma and gastric mucosa was characterized by liquid chromatography-mass spectrometer-based lipidomic analysis.
PQS+DAPT further decreased platelet aggregation, lessened infarction and attenuated cardiac injury compared with DAPT. Plasma lipidomic analysis revealed significantly increased synthesis of epoxyeicosatrienoic acid (EET) and prostaglandin (PG) I (potent inhibitors for platelet adhesion and aggregation) while markedly decreased thromboxane (TX) A (an agonist for platelet activation and thrombosis) by PQS+DAPT, relative to DAPT. DAPT induced overt gastric mucosal damage, which was attenuated by PQS co-administration. Mucosal gastroprotective PGs (PGE, PGD and PGI) were consistently increased after supplementation of PQS+DAPT.
Collectively, PQS+DAPT showed synergistic effect in platelet inhibition with ameliorated MI expansion partially through upregulation of AA/EET and AA/PGI synthesis while suppression of AA/TXA metabolism. PQS attenuated DAPT-induced gastric injury, which was mechanistically linked to increased mucosal PG production.
研究表明，西洋参总皂苷（PQS）可抑制血小板黏附，对胃具有保护作用。本研究旨在探讨 PQS 与双联抗血小板治疗（DAPT）联合应用对急性心肌梗死（AMI）大鼠模型血小板聚集、心肌梗死扩大和胃损伤的综合疗效，并探讨其与花生四烯酸（AA）衍生的类二十烷酸代谢相关的机制。
结扎左冠状动脉诱导 Wistar 大鼠 AMI 模型，随后给予 DAPT、PQS 或联合治疗。采用透光比浊法测定血小板聚集。采用 TTC 和 H&E 染色分别评估梗死面积和心肌组织病理学。通过扫描电子显微镜（SEM）观察胃黏膜损伤。采用基于液相色谱-质谱的脂质组学分析方法对血浆和胃黏膜中的类二十烷酸谱进行全面分析。
与 DAPT 相比，PQS+DAPT 进一步降低了血小板聚集，减轻了梗死面积，减轻了心脏损伤。血浆脂质组学分析显示，PQS+DAPT 显著增加了环氧二十碳三烯酸（EET）和前列腺素（PG）I（血小板黏附和聚集的有效抑制剂）的合成，同时明显减少了血栓素（TX）A（血小板激活和血栓形成的激动剂）的合成。与 DAPT 相比，DAPT 诱导了明显的胃黏膜损伤，而 PQS 联合给药则减轻了这种损伤。联合应用 PQS+DAPT 后，胃黏膜保护性 PG（PGE、PGD 和 PGI）持续增加。
总之，PQS+DAPT 在抑制血小板方面具有协同作用，改善了心肌梗死的扩大，部分通过上调 AA/EET 和 AA/PGI 的合成，同时抑制 AA/TXA 代谢来实现。PQS 减轻了 DAPT 引起的胃损伤，其机制与胃黏膜 PG 生成增加有关。
