Abstract
ObjectivesPrevious studies have found that Panax quinquefolius saponins (PQS) combined with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel enhances antithrombotic effects while reducing gastric mucosal injury induced by DAPT. We investigated the effects of the combined drug therapy (PQS+DAPT) through the COX/PG pathways.MethodsAcute myocardial infarction (AMI) was induced in Wistar rats by ligation of the left anterior descending (LAD) coronary artery, and the animals were randomly divided into Model, DAPT, and PQS+DAPT groups. Rats in the sham group did not undergo artery ligation. They were intragastrically treated for 14 days. Myocardial infarct size; myocardial pathology; platelet aggregation rate, CD62p activation, concentrations of thromboxane B2 (TXB2), 6-keto-PGF1α, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI), the TXB2/6-keto-PGF1α ratio were measured. The ultrastructure of the gastric mucosa was observed by scanning electron microscopy. The expression of PGE2 and 6-keto-PGF1α in gastric mucosa was measured by radioimmunoassay, and levels of COX-1, COX-2, and VEGF in gastric mucosa were assessed using immunohistochemistry.ResultsThe addition of Panax quinquefolius saponins (PQS+DAPT) to standard DAPT therapy significantly decreased the myocardial infarct area, degree of myocardial lesions, TXB2 and PAI levels, and the TXB2/6-keto-PGF1α ratio, while increasing 6-keto-PGF1α and t-PA levels and reducing the degree of gastric mucosal injury. Expression of PGE2, 6-keto-PGF1α, COX-2, and VEGF in the gastric mucosa was upregulated in the PQS+DAPT group compared with the standard DAPT group.ConclusionPQS increases the degree of DAPT inhibition of myocardial necrosis and antiplatelet effects in AMI rats, as well as reducing damage to the gastric mucosa caused by DAPT. The mechanism may be related to inhibition of TXB2 and PAI activity and elevation of 6-keto-PGF1α and t-PA levels in blood, and may be associated with upregulated expression of COX-2, PGE2, PGI2, and VEGF in gastric tissue.
Highlights
Dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel is the standard regimen for acute coronary syndrome (ACS) patients and patients who have undergone percutaneous coronary intervention (PCI) [1]
The present study found that DAPT therapy could reduce pathological damage from myocardial infarction in rats and effectively inhibit platelet activation, and that DAPT damages gastric mucosa by inhibiting the expression of COX-1, COX-2, prostaglandin E2 (PGE2), PGI2, and vascular endothelial growth factor (VEGF)
Our results suggest that DAPT therapy significantly inhibited platelet activation, while exerting no notable effects on the fibrinolytic system, and Panax quinquefolius saponins (PQS) enhances the antithrombotic effects of DAPT therapy by increasing aspirin inhibition of the COX-1/thromboxane A2 (TXA2) pathway in platelets, improving the TXA2/PGI2 balance, and activating the fibrinolytic system
Summary
Dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel is the standard regimen for acute coronary syndrome (ACS) patients and patients who have undergone percutaneous coronary intervention (PCI) [1]. Side effects from drug therapy are important factors related to poor prognosis of coronary heart disease (CHD) [4]. Achieving effective antiplatelet action while avoiding gastrointestinal damage or hemorrhage has become a focal point in selecting among treatments for patients with cardiovascular thrombotic disease. Aspirin is a non-steroidal drug, and can directly injure gastric mucosa and inhibit the activities of COX-1 and COX-2, leading to a reduction in prostaglandin (PG) and subsequently influence the regulation of gastrointestinal blood flow and mucous functions and weakening the gastric mucus bicarbonate barrier [6]. Clopidogrel, an adenosine diphosphate receptor antagonist, does not directly damage the digestive tract mucosa, but can inhibit platelet-derived growth factor (PDGF) and platelets from releasing vascular endothelial growth factor (VEGF), which blocks the neovascularization and subsequent repair of gastrointestinal mucosa [7]
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