CAJ | 학술논문

目的：观察负荷量氯吡格雷对脂多糖诱导的脓毒症大鼠血小板聚集和肺组织炎症损伤的影响。方法36只雄性Wistar大鼠随机分为对照组、脓毒症组、氯吡格雷组，每组12只。对照组大鼠腹腔注射生理盐水10 mg/kg；脓毒症组大鼠予腹腔注射脂多糖建立脓毒症/急性肺损伤（ALI）模型；氯吡格雷组大鼠在腹腔注射脂多糖后立即给予氯吡格雷800 mg/kg灌胃，建模后3 h，取血测量动脉血氧分压（PaO2），计算氧合指数（PaO2/FiO2），运用全血电阻法测定血小板聚集率，用酶联免疫分析法测量血及肺组织中肿瘤坏死因子-α（ TNF-α）浓度，取肺组织HE染色观察肺组织病理，并计算肺湿/干重比值（ W/D比值）。结果脓毒症组、氯吡格雷组PaO2、PaO2/FiO2均低于对照组（P＜0．05）；但氯吡格雷组PaO2、PaO2/FiO2均明显高于脓毒症组（P＜0．05）。脓毒症组、氯吡格雷组大鼠肺湿/干重比值、血清及肺组织TNF-α均高于对照组（P均＜0．05），但氯吡格雷组上述指标均明显低于脓毒症组（P均＜0．05）。氯吡格雷组血小板聚集率明显低于另外两组（P＜0．05）。脓毒症组大鼠肺组织可见明显炎症损伤，氯吡格雷组肺组织炎性损伤程度明显减少。结论负荷量氯吡格雷可迅速抑制脓毒症大鼠急性肺损伤血小板的活化和聚集，并减轻肺组织炎症损伤。
목적：관찰부하량록필격뢰대지다당유도적농독증대서혈소판취집화폐조직염증손상적영향。방법36지웅성Wistar대서수궤분위대조조、농독증조、록필격뢰조，매조12지。대조조대서복강주사생리염수10 mg/kg；농독증조대서여복강주사지다당건립농독증/급성폐손상（ALI）모형；록필격뢰조대서재복강주사지다당후립즉급여록필격뢰800 mg/kg관위，건모후3 h，취혈측량동맥혈양분압（PaO2），계산양합지수（PaO2/FiO2），운용전혈전조법측정혈소판취집솔，용매련면역분석법측량혈급폐조직중종류배사인자-α（ TNF-α）농도，취폐조직HE염색관찰폐조직병리，병계산폐습/간중비치（ W/D비치）。결과농독증조、록필격뢰조PaO2、PaO2/FiO2균저우대조조（P＜0．05）；단록필격뢰조PaO2、PaO2/FiO2균명현고우농독증조（P＜0．05）。농독증조、록필격뢰조대서폐습/간중비치、혈청급폐조직TNF-α균고우대조조（P균＜0．05），단록필격뢰조상술지표균명현저우농독증조（P균＜0．05）。록필격뢰조혈소판취집솔명현저우령외량조（P＜0．05）。농독증조대서폐조직가견명현염증손상，록필격뢰조폐조직염성손상정도명현감소。결론부하량록필격뢰가신속억제농독증대서급성폐손상혈소판적활화화취집，병감경폐조직염증손상。
Objective To observe the effects of loading dose of clopidogrel on platelet aggregation in sepsis and inflammatory reaction of lung tissues in acute lung injury ( ALI ) induced by lipopolysaccharide .Methods Thirty-six male Wistar rats were divided randomly into 3 groups ( 12 rats in each group ):control group ( group N ) , model group (group L) and clopidogrel treatment group(group T).The rats in group N received normal saline at the dose of 10 mg/kg by intra-peritoneal injection;The rats in group L received lipopolysaccharide by intra-peritoneal injection to establish sepsis/ALI rat model;The rats in group T were oral administered with clopidogrel at the dose of 800 mg/kg immediately after injection of lipopolysaccharide.In the 3rd hour after lipopolysaccharide injection ,blood samples were collected to measure PaO 2 ,and artery blood gases oxygenation index ( PaO2/FiO2 ) was analyzed .Platelet aggregation was assayed by impedance platelet aggregometry ,and the levels of tumor necrosis factor-α( TNF-α) in lung tissue and serum were measured by enzyme-linked immunosorbent assay .HE staining was used to observe the pathological changes of lung tissues ,and the wet and dry ratio(W/D ratio) of the lung was calculated.Results PaO2,PaO2/FiO2 in group L,group T were lower than those in group N( P<0.05);PaO2 ,PaO2/FiO2 in group T was significantly higher than those in group L ( P<0.05) .The W/D ratio of the lung ,levels of TNF-αin lung tissue and serum in group L ,group T were significantly higher than those in group N(all P<0.05),which were significantly lower in group T in contrast with those in group L (all P<0.05).The ratio of platelet aggregation in group T was significantly lower than that in group N or group L (P <0.05).The obvious inflammatory reaction of lung tissues was observed in the rats of group L while the less inflammatory reaction of lung tissues was observed in group T .Conclusion The loading dose of clopidogrel can suppress the aggregation and activation of platelet in sepsis rats with ALI rapidly ,as well as relieve the inflammation reaction of lung tissues .