氯吡格雷预处理对脓毒症大鼠心肌损伤保护作用及机制的研究

目的探讨氯吡格雷干预对血小板聚集及脓毒症心肌损伤的影响及脓毒症时心肌损伤与血小板的聚集的关系。方法取Wistar雄性大鼠72只,随机分成3组：正常对照组（NC组）,内毒素组（ET组）,氯吡格雷＋内毒素组（CL＋ET组）。CL＋ET组预先给予氯吡格雷3 d后,腹腔注射LPS（10 mg·kg-1）建立急性脓毒症心肌损伤模型。在0、6、12 h采血检测血小板聚集率、心肌肌钙蛋白I（cTnI）；酶联免疫吸附测定法（ELISA）检测血清、心肌中TNF-α的表达水平；检测心脏干湿重比；取心肌标本,行HE染色,光镜观察大鼠心肌结构改变。结果与NC组相比,注射LPS后ET组血小板聚集率更高（P〈0.05）,且随时间延长而增加（27.78±1.01）、（32.41±3.04）、（50.99±14.35）ohm]；CL＋ET组预先给予氯吡格雷处理后,血小板聚集率处于抑制状态（P〈0.05）。CL＋ET组较ET组,在相应时点对内毒素诱导的cTnI、血清及心肌TNF-α水平升高有明显的抑制作用（P〈0.05）；心肌干湿重比有差异（P〈0.05）。ET组LPS注射6 h后心肌出现炎症细胞浸润、纤维肿胀、排列紊乱,12 h最显著；与ET组比较,CL＋ET组在相应时点对心肌炎症细胞浸润和心肌纤维肿胀程度减轻。结论 LPS引起的心肌损伤过程中血小板聚集明显,氯吡格雷阻断血小板P2Y12受体,抑制血小板聚集,对LPS引起的心肌损伤具有一定的抑制作用。

Myocardial protective effects of clopidogrel preconditioning in septic rats

Objective To explore the effect of clopidogrel preconditioning on platelet aggregation and myocardial injury,so as to investigate the relationship of platelet aggregation and myocardial injury in sepsis. Methods Seventy-two Wistar rats were randomly assigned into three groups： normal control group（ NC,n = 24）,endotoxin group（ ET,n = 24）,clopidogrel pretreatment and endotoxin group（ CL ＋ ET,n = 24）. Rats in ET group and CL ＋ ET group were injected intraperitineally with LPS（10 mg·kg-1） to establish an acute cardiac injury model,then continuous intragastric administration of clopidogrel were administered for three days. Each group was observed at three time point（0,6,12 h,n = 8）. Platelet aggregation was tested with impedance platelet aggregometry;cTnI in blood was determined with che ＋ luminescent technique;the expressions of TNF-α in blood and cardiac myocytes were measured with enzymelinked immunoadsorbent assay（ ELISA） kits;myocardial tissues were determined with dry and wet weight;myocardial pathological damage was observed under the light at certain time（0h,6,12h）. Results Compared with NC group,platelet aggregation was increased apparently in ET group（ P 〈 0. 05） and gradually（27. 78 ± 1. 01）,（32. 41 ± 3. 04）,（50. 99 ± 14. 35）]ohm;platelet aggregation in CL ＋ ET was lower（ P 〈0. 05）. Compared with ET group,CL ＋ ET group markedly inhibited the increasement of cTnI,TNF-αin blood and cardiac myocytes（ P 0. 05）;the dry and wet weight of myocardial tissues had difference（ P 〈0. 05）. The myocardial damage could be observed in 6h ET subgroup by light microscopy：the inflammatory cells were infiltrated,the fibrilla of myocardial cell were swelled, their cristae were disrupted,and the most severe myocardial damage could be observed with time going by. Conclusions Clopidogrel may inhibit platelet aggregation by blocking platelet P2Y12 receptor and then alleviate the LPS myocarditis.