CAJ | 학술논문

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。
목적：탐토록필격뢰간예대혈소판취집급농독증심기손상적영향급농독증시심기손상여혈소판적취집적관계。방법취Wistar웅성대서72지，수궤분성3조：정상대조조（ NC조），내독소조（ ET조），록필격뢰＋내독소조（ CL＋ET조）。 CL＋ET조예선급여록필격뢰3 d후，복강주사LPS（10 mg· kg-1）건립급성농독증심기손상모형。재0、6、12 h채혈검측혈소판취집솔、심기기개단백I（ cTnI）；매련면역흡부측정법（ ELISA）검측혈청、심기중TNF-α적표체수평；검측심장간습중비；취심기표본，행HE염색，광경관찰대서심기결구개변。결과여NC조상비，주사LPS후ET조혈소판취집솔경고（ P＜0．05），차수시간연장이증가[（27．78±1．01）、（32．41±3．04）、（50．99±14．35）ohm]；CL＋ET조예선급여록필격뢰처리후，혈소판취집솔처우억제상태（ P＜0．05）。 CL＋ET조교ET조，재상응시점대내독소유도적cTnI、혈청급심기TNF-α수평승고유명현적억제작용（P＜0．05）；심기간습중비유차이（P＜0．05）。 ET조LPS주사6 h후심기출현염증세포침윤、섬유종창、배렬문란，12 h최현저；여ET조비교，CL＋ET조재상응시점대심기염증세포침윤화심기섬유종창정도감경。결론 LPS인기적심기손상과정중혈소판취집명현，록필격뢰조단혈소판P2Y12수체，억제혈소판취집，대LPS인기적심기손상구유일정적억제작용。
Objective To explore the effect of clopidogrel preconditioning on platelet aggregation and myocardial injury ,so as to investi-gate 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 ob-served 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-αin blood and cardiac myocytes were measured with enzyme-linked immunoadsorbent assay ( ELISA) kits;myocardial tissues were determined with dry and wet weight;myocardial pathological dam-age 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 P 2Y12 receptor and then alleviate the LPS myocarditis .