原创力文档clopidogrel, a p2y12 receptor antagonist, potentiates the inflammatory response in a rat model of peptidoglycan polysaccharide-induced arthritisp2y12受体拮抗剂氯吡格雷,强化的炎症反应在老鼠模型中肽聚糖polysaccharide-induced关节炎.pdfVIP
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clopidogrel, a p2y12 receptor antagonist, potentiates the inflammatory response in a rat model of peptidoglycan polysaccharide-induced arthritisp2y12受体拮抗剂氯吡格雷,强化的炎症反应在老鼠模型中肽聚糖polysaccharide-induced关节炎
Clopidogrel, a P2Y12 Receptor Antagonist, Potentiates
the Inflammatory Response in a Rat Model of
Peptidoglycan Polysaccharide-Induced Arthritis
1,2 . 1.¤ 1 1,2 1,2,3
Analia E. Garcia * , Sripal R. Mada , Mario C. Rico , Raul A. Dela Cadena , Satya P. Kunapuli
1 Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Temple University Hospital, Philadelphia, Pennsylvania, United States of America,
2 Department of Physiology, Temple University School of Medicine, Temple University Hospital, Philadelphia, Pennsylvania, United States of America, 3 Department of
Pharmacology, Temple University School of Medicine, Temple University Hospital, Philadelphia, Pennsylvania, United States of America
Abstract
The P2Y12 receptor plays a crucial role in the regulation of platelet activation by several agonists, which is irreversibly
antagonized by the active metabolite of clopidogrel, a widely used anti-thrombotic drug. In this study, we investigated
whether reduction of platelet reactivity leads to reduced inflammatory responses using a rat model of erosive arthritis. We
evaluated the effect of clopidogrel on inflammation in Lewis rats in a peptidoglycan polysaccharide (PG-PS)-induced
arthritis model with four groups of rats: 1) untreated, 2) clopidogrel-treated, 3) PG-PS-induced, and 4) PG-PS-induced and
clopidogrel-treated. There were significant differences between the PG-PS+clopidogrel group when compared to the PG-PS
group including: increased joint diameter and clinical manifestations of inflammation, elevated plasma levels of pro-
inflammatory cytokines (IL-1 beta, interferon (IFN) gamma, and IL-6), an elevated neutrophil bl
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