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The enhanced protective effort and mechanism of aspirin by clopidogrel in myocardial injury rats |
Chen Wei-cheng, Rui Lei, Deng Yun-xi, Wen Han-chun, Zhu Ji-jin |
Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China |
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Abstract Objective The present study aims to investigate the protective effect and its related mechanism of dual antiplatelet combined aspirin and clopidogrel in LPS-induced myocardial injury with rats. Methods Forty male Wistar rats were randomly divided into five groups: the control group, LPS group, aspirin group, clopidogrel group, aspirin plus clopidogrel group(n=8), 8 rats are contained in each group. The rats in control and LPS group were respectively treated with 1 mL normal saline, whilerats in aspirin clopidogrel and dual antiplatelet group were respectively given by aspirin(100 mg/kg),clopidogrel(200 mg/kg), aspirin(100 mg/kg)+clopidogrel(200 mg/kg), achieved pretreatment through gavage for three days. After that, in addition to the control group, the remaining group was administered with LPS(10 mg/kg)through the enterocoelia. Six hours after modeling, specimens were collected for analysis. The ejection fraction, cardiac output, left ventricular end diastolic diameter and left ventricularend systolic diameter were measured by UCG. The concentration of serum cardiac troponin, tumor necrosis factor-α and IL-6, platelet aggregation rate were determined; and the expression of platelet membrane glycoprotein CD62P and toll-like receptors were measured by flow cytometry; myocardial tissue dry wet weight ratio was measured; myocardial tissue pathology through the light microscope was observed. Results Inflammatory cells infiltration, edema and congestion in myocardial mesenchyma tissue in LPS group were found, and the severity of myocardial tissue inflammation were reduced in the intervention groups compared with the LPS group, especially obvious in the dual antiplatelet group. The level of EF and myocardial tissue dry/wet ratio were decreased while the level of serum cTnI, TNF-α, IL-6, CO, left ventricular end diastolic diameter and ventricular end systolic diameter, platelet aggregation,the expression of platelet CD62P, TLR-4 were significantly increased in LPS group compared with the control group(P<0.01). Drug pretreatment group can reduced those changes, especially the dual antiplatelet group combined aspirin and clopidogrel(P<0.01). Conclusion The level of LPS- induced myocardial injury could be significantly reduced by the dual antiplatelet combined by aspirin and clopidogrel, which playing a role in inhibiting of production of TNF-α, IL-6 and the excessive of platelet activation and aggregation.
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Corresponding Authors:
Zhu Ji-jin, E-mail: zhujijin63@vip.sina.com
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