| Objective:To observe the effects of aspirin and clopidogrel dual antiplatelet on platelet function in sepsis rats and acute lung injury.Methods:40 healthy male wistar rats were randomly divided into five groups (8 rats in each group):control group (N group), endotoxin group (LPS group), aspirin group (A group), clopidogrel group (C group), aspirin plus clopidogrel group (A +C group). The rats in N group and LPS group were respectively treated with normal saline 1ml while A group, C group,A+C group were respectively given aspirin (100mg/kg), clopidogrel (200mg/kg), aspirin (100mg/kg)+clopidogrel (200mg/kg) gavaged three days, after which, apart from the control group, the remaining groups were given LPS lOmg/kg by intraperitoneal injection. HE staining was used to observe the pathological changes of lung tissue. And the wet and dry ratio of the lung was calculated. Arterial blood samples were collected to measure PaO2, then calculated oxygenation index (PaO2/FiO2).The expression level of platelet CD62P and TLR4 were measured by flow cytometry instrument, the concentration of TNF-a and IL-6 in serum were measured by ELISA, platelet aggregation was assayed by the whole blood electrical impedance aggregometry.Results:1.The general expressionism of rats:There were no significantly changes in the N group. Rats in LPS group breathing rapidly, loss of appetite, listlessness, less dynamic, nose and mouth secretions, stimulate poor response. Compared with LPS group,the above symptoms still existed, but the symptoms has relieved significantly in A group, C group, A+C group. Rats in N group and A+C group were no deaths, LPS group died two, A group and C group each have one rat died.2.Lung pathological changes:N group showed no abnormal changes in lung tissue structure.In LPS group,the alveolar was ruptured and deformed, the alveolar septum was broadened,and there was a large number of inflammatory cells infiltrating in alveoli and interstitial.Compared with LPS group,the severity of pulmonary pathological injury induced by LPS was reduced in A group,C group,A+C group.In drug intervention groups,the least inflammatory reaction was found in A+C group,and the degree of inflammatory was lower than the A group or C group.3.The changes of PaO2,PaO2/FiO2,lung W/D ratio in each group: PaO2,PaO2/FiO2 in LPS group were lower than those in N group (P<0.01); PaO2,PaO2/FiO2 in A group,C group,and A+C group were significantly higher than those in LPS group (P<0.05).Lung W/D in LPS group were significantly higher than that in N group(P<0.01), which were significantly lower in A groups,C group,A+C group contrast with that in LPS group(P<0.05).Compared with the monotherapy group A or group C, the PaO2,PaO2/FiO2 were higer and lung W/D ratio lower in A+C group (P<0.05).4.The changes of serum TNF-a and IL-6 levels:In LPS group the serum concentrations of TNF-α and IL-6 were higher than these in N group(P<0.01), meanwhile that in A group, C group,A+C group were lower than these in LPS group (P<0.05).The level of TNF-a and IL-6 in serum in A+C group were the lowest among the LPS group,A group,C group,A+C group.5.The changes of platelet aggregation,paltelet CD62P and TLR4:The expression of platelet aggregation, platelet CD62P and TLR4 in LPS group were significantly higher than those in N group (P<0.01). platelet aggregation, platelet CD62P and TLR4 in intervention groups were lower than those in LPS group(P<0.05).The most obvious change was occured in group A+C.Conclusion:Platelet activation was enhanced in the process of sepsis with acute lung injury. Joint use of aspirin and clopidogrel could alleviate the extent of acute lung injury.The mechanism may be related to inhibit the excessive activation of platelet, thereby inhibiting platelet activation mediated by inflammation reaction... |
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