Effects Of Clopidogrel On Platelet Aggregation In Sepsis And Acute Lung Injury Induced By Lipopolysaccharide

AIM: To investigate the platelet aggregation function， blood gasesoxygenation index (PaO2/FiO2), lung tissue and serum TNF-α levels, lungconfiguration and lung tissue wet-dry weight ratio (W/D ratio) changes inducedby block platelet P2Y12receptor in sepsis rat. As well as, to explore the potentialintervention mechanism of clopidogrel on acute lung injury induced bylipopolysaccharide(LPS).METHODS:1.Animal grouping: A total36healthy Wistar male rats, aged8weeks, weight about250g, were randomly divided into3groups(n=12):Ngroup(control group), L group(model group), T group(clopidogrel treatmentgroup).2. Animal model: The rats in N group were received normal saline at thedose of2ml/kg by intra-peritoneal (i.p.) injection, the ALI rat model wasestablished by i.p. injection of LPS (10mg/kg), the rats in T group were oraladministered by clopidogrel at the dose of800mg/kg immediately after injectionof LPS.3. Specimens drawn: All the rats were anesthetized at3hours after theLPS injection. Blood samples were collected and artery blood gases oxygenationindex (PaO2/FiO2) was analyzed. Platelet aggregation was assayed byimpedance platelet aggregometry, and the levels of TNF-α in lung tissue andserum were measured by enzyme-linked immunosorbent assay. At same timepoints, the following parameters were assayed: pathological examinations andthe wet-dry weight ratio (W/D ratio) of lung tissue.RESULTS:1. Artery blood gases oxygenation index: In L group and T group, PaO2and PaO2/FiO2were significantly lower than in N group(p＜0.05),PaO2and PaO2/FiO2in T group were significantly higher than in L group(p＜0.05), but did not reach the level of N group.2. Pathological observation of lung tissue: N group showed no abnormalchanges in lung tissue structure. In L group, there was a mass of infiltration ofneutrophils and red cells in the alveoli and alveolar septum. The alveolar spacewas narrowed, partial alveolar space filled with pink edematous fluid. Inaddition, the alveolar walls burst and the alveolar septum was broadened.However, the severity of pulmonary pathological injury induced by LPS wasreduced in T group, there was less PMN cells infiltration, wider alveolar spacecomparison with the lung of rats in L group.3. Lung tissue wet-dry weight ratio (W/D ratio): The W/D ratio of lungtissue in L group and T group were higher than in N group, and the W/D ratio oflung tissue in T group was significantly lower than that in L group (p <0.05).4. Platelet aggregation change: The platelet aggregation in L group weresignificantly higher than in N group (p<0.05), and that in T group wassignificantly lower than those in N group and L group (p <0.05).5. Serum and lung tissue TNF-α level: In L group and T group, the serumconcentrations of TNF-α were higher than that in N group (p <0.05), meanwhilethat in T group was lower than in L group (p <0.05). The level of TNF-α in thelung tissue in L group and T group was higher than that in N group (p <0.05),and that in T group was significantly lower than in L group (p <0.05).CONCLUSIONS: Clopidogrel could relieve the inflammation reactioninduced by LPS and improve lung function in sepsis. Which might be relate to inhibit platelet P2Y12receptor, decrease serum TNF-α and lung tissue TNF-α.