阿司匹林、氯吡格雷、西洛他唑抗血栓形成作用及其机制的研究

Anti-thrombosis effects of aspirin,clopidogrel and cilostazol

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7 d;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（c AMP）、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c AMP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c AMP及下调TXA2及PDEⅢ水平。

Objective To explore the anti-thrombosis effects of aspirin,clopidogrel,cilostazol. Methods A total of70 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 c AMP,TXA2 and PDEⅢ level 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 suppression 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 prolonged,maximum agglutination of platelet decreased,formation of thrombus suppression rate increased,blood c AMP level increased,TXA2 and PDEⅢ decreased（ 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 inhibit platelet aggregation,reduce thrombosis,which may be related to the decrease of platelet aggregation,up-regulate the blood c AMP,down-regulate TXA2 and PDEⅢ.