CAJ | 학술논문

目的：观察常用抗血小板药物阿司匹林、氯吡格雷、西洛他唑的抗血栓形成作用，并探讨其机制。方法将70只SD大鼠随机分成7组各10只，其中对照组不做特殊处理；模型组、阿司匹林组、氯吡格雷组、西洛他唑组、三联组均制备冠状动脉微栓塞模型，建模成功后分别灌服安慰剂、阿司匹林、氯吡格雷、西洛他唑及阿司匹林＋氯吡格雷＋西洛他唑，连续7d；假手术组在冠状动脉微栓塞模型制作中以生理盐水代替血栓微粒注入左心室，术后灌服安慰剂。实验期间各组均经腹主动脉取血，用自动血凝分析仪分别测定凝血参数凝血酶原时间（ PT）、活化部分凝血活酶时间（APTT）和凝血酶时间（TT），采用血小板聚集率检测仪在6μmol/L的腺苷二磷酸（ADP）诱导下测量最大血小板聚集率，采用ELISA法测定环腺苷酸（cAMP）、血栓素A2（TXA2）和Ⅲ型磷酸二酯酶（PDEⅢ）水平；实验结束后，将各组大鼠仰卧固定消毒、麻醉，采用左颈外静脉、右颈总动脉置入聚乙烯管法检测血栓形成抑制率。结果与模型组比较，4个用药组PT、APTT及TT均明显延长，血小板聚集率明显降低，血栓形成抑制率显著升高，血浆cAMP显著升高、TXA2及PDEⅢ显著降低，尤以三联组为著（P均＜0．01）。实验第3～7天假手术组、阿司匹林组、氯吡格雷组和三联组上述凝血参数均无统计学差异。结论阿司匹林、氯吡格雷、西诺他唑均可抑制血栓形成，三者联用具有协同增效作用；主要作用机制包括减少血小板聚集、上调血浆cAMP及下调TXA2及PDEⅢ水平。
목적：관찰상용항혈소판약물아사필림、록필격뢰、서락타서적항혈전형성작용，병탐토기궤제。방법장70지SD대서수궤분성7조각10지，기중대조조불주특수처리；모형조、아사필림조、록필격뢰조、서락타서조、삼련조균제비관상동맥미전새모형，건모성공후분별관복안위제、아사필림、록필격뢰、서락타서급아사필림＋록필격뢰＋서락타서，련속7d；가수술조재관상동맥미전새모형제작중이생리염수대체혈전미립주입좌심실，술후관복안위제。실험기간각조균경복주동맥취혈，용자동혈응분석의분별측정응혈삼수응혈매원시간（ PT）、활화부분응혈활매시간（APTT）화응혈매시간（TT），채용혈소판취집솔검측의재6μmol/L적선감이린산（ADP）유도하측량최대혈소판취집솔，채용ELISA법측정배선감산（cAMP）、혈전소A2（TXA2）화Ⅲ형린산이지매（PDEⅢ）수평；실험결속후，장각조대서앙와고정소독、마취，채용좌경외정맥、우경총동맥치입취을희관법검측혈전형성억제솔。결과여모형조비교，4개용약조PT、APTT급TT균명현연장，혈소판취집솔명현강저，혈전형성억제솔현저승고，혈장cAMP현저승고、TXA2급PDEⅢ현저강저，우이삼련조위저（P균＜0．01）。실험제3～7천가수술조、아사필림조、록필격뢰조화삼련조상술응혈삼수균무통계학차이。결론아사필림、록필격뢰、서낙타서균가억제혈전형성，삼자련용구유협동증효작용；주요작용궤제포괄감소혈소판취집、상조혈장cAMP급하조TXA2급PDEⅢ수평。
Objective To explore the anti-thrombosis effects of aspirin, clopidogrel, cilostazol.Methods A total of 70 SD rats were involved in this study and equally divided into 7 groups with 10 rats in each group.Rats in control group did not deal with any special processe.Rats in model group, aspirin group, clopidogrel group, cilostazol group and triad group were made coronary artery microembolization model, then rats in above groups were drenched 7 days with placebo, aspirin, clopidogrel, cilostazol and aspirin+clopidogrel+cilostazol, respectively.Abdominal aortic blood PT, APTT and TT were detected by automatic blood coagulation analyzer.Maximum agglutination of platelet was detected under the induce of ADP by the platelet aggregation rate tester.Blood cAMP, TXA2 and PDEⅢlevel were tested by the method of ELISA. After the blood test, all rats in each group were anaesthetized at dorsal decubitus to detect the formation of thrombus sup-pression rate by polyethylene tube method through left external jugular vein and right common carotid artery.Results Compared with model group, some observe indicator of 4 drug groups significant changed, including PT, APTT and TT pro-longed, maximum agglutination of platelet decreased, formation of thrombus suppression rate increased, blood cAMP level increased, TXA2 and PDEⅢdecreased ( all P<0.01) .Coagulation parameters of sham group, aspirin group, clopidogrel group, cilostazol group and triad group were no significance.Conclusions Aspirin, clopidogrel and cilostazol can also in-hibit platelet aggregation, reduce thrombosis, which may be related to the decrease of platelet aggregation, up-regulate the blood cAMP, down-regulate TXA2 and PDEⅢ.