The Relationship Between Platelets Activation And Myocardial Injury Induced By LPS In Rats And The Protective Effort Of Aspirin Enhancedby Clopidogrel

AIM:The aim of this study was to investigate the underlying mechanismsof platelet activation in LPS-induced myocardial injury and the protective effect of aspirin and clopidogrel.METHODS:Forty male wistar rats were randomly divided in double-blind manner into five groups: the control group,LPS group, aspirin group,clopidogrel group,aspirin plus clopidogrel group(n=8), The rats in control and LPS group were respectively treated with normal saline 1ml while aspirin? clopidogreland duala antiplatelet group ,were respectively given by aspiri(100mg/kg),clopidogrel(200mg/kg), aspirin (100 mg/kg)+clopidogrel (200mg/kg),achieved pretreatment through gavage for three days. After that ,in addition to the control group,the remaining group were administered with LPS(10mg/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 ventricular end systolic diameter were measured by UCG , the concentration of serum cardiac troponin? tumor necrosis factor-? 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:1.The rats behavioral expressionThere were no significantly changes in the control group. Rats in LPS group had mental fatigue, insensitive, less dynamic, gregarious, dull coat, shaggy hair ,unhairing and convulsion, and the symptoms became worse as time goes by.Compared with the control group, the changes of behavioral expression of rats in the intervention groups were started after injected intraperitineally with LPS,but somewhat less severe than those in the LPS group,especially in the dual antiplatelet group.2.The pathomorphological changes of rats myocardial tissue under light microscopeFlammatory 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.3. The comparison ofleft ventricular end diastolic diameter and Left ventricular end systolic diameter were changes in each group.The left ventricular end diastolic diameter and Left ventricular end systolic diameterwereincreased after injected intraperitineally with LPS,and,the intervention groupswere less increased than those in the LPS group,especially in the dual antiplatelet group.4.The comparison of serum cTnI and EF?CO in each group.The level of EF were decreased while the level of cTnI CO were significantly increased in LPS group compared with the control group (P<0.01).Single antiplatelet agent aspirin or clopidogrel can reduced those changes,but dual antiplatelet combined aspirin and clopidogrel showed more obvious anti-inflammatory effort than single agent(P<0.01).5.The comparison of serumTNF-?, IL-6 and dry-wet weight ratios of myocardial tissuesin each group.The levelmyocardial tissue D/W ratio were decreased while the level of serum TNF-?, IL-6 were significantly increased in LPS group compared with the control group (P <0.01).Single antiplatelet agent aspirin or clopidogrel can reduced those changes, but dual antiplatelet combined aspirin and clopidogrel showed more obvious anti-inflammatory effort than single agent(P<0.01).6.The comparison of platelet aggregationandthe expression of platelet CD62P,TLR4in each group.The level of platelet aggregation and the expression of platelet CD62P,TLR4 were significantly increased in LPS group compared with the control group (P <0.01).Single antiplatelet agent aspirin or clopidogrel can reduced those changes, but dual antiplatelet combined aspirin and clopidogrel showed more obvious anti-inflammatory effort than single agent(P<0.01).CONCLUSIONS:1. Platelet activation participate in LPS-induced myocardial injury by means of releasing inflammatory factor.2. LPS-induced myocardial injury could be significantly reduced by the Dual antiplatelet of combination of aspirin and clopidogrel than single agent,and the possible mechanism is to inhibit the activation of platele which induced by LPS.