氧化三甲胺对氯吡格雷抗血小板聚集的抑制作用观察  

Inhibitory effect of TMAO on anti-platelet aggregation effects of clopidogrel

作　　者：马瑞松 胡小春 王苗[1] 廖旺[1] 王圣[1] MA Ruisong;HU Xiaochun;WANG Miao;LIAO Wang;WANG Sheng(Department of Cardiology,Hainan General Hospital,Haikou 570311,China)

机构地区：[1]海南省人民医院心内科海南省心血管病临床研究中心,海口570311

出　　处：《山东医药》2022年第33期9-12,共4页Shandong Medical Journal

基　　金：海南省自然科学基金项目(821MS0823,822RC811)。

摘　　要：目的观察氧化三甲胺(TMAO)对氯吡格雷(Clo)抗血小板聚集的抑制作用。方法19只雄性SD大鼠随机分为IR组、Clo+IR组、TMAO+Clo+IR组。IR组制备IR模型;Clo+IR组使用Clo溶液灌胃4 d后再制作IR模型;TMAO+Clo+IR组使用Clo溶液灌胃4 d,尾静脉注射TMAO溶液后再制作IR模型。取大鼠颈静脉血,使用全自动血液体液分析仪测定血小板计数、平均血小板体积(MPV)、大血小板比例(P-LCR),使用血小板聚集功能分析仪观察血小板聚集功能,包括最大聚集率(MaxAR-ADP)、平均聚集率(AveAR-ADP)和最大聚集时间(MaxAT-ADP)。再灌注4 h后断尾,观察大鼠断尾出血时间。采用免疫染色法观察大鼠心肌血栓负荷,用最大血栓浓度(MD)和血栓指数(TI)表示。结果Clo+IR组血小板计数显著高于IR组(P<0.05)。Clo+IR组、TMAO+Clo+IR组血小板MaxAR-ADP、AveAR-ADP均低于IR组(P均<0.05),而TMAO+Clo+IR组血小板MaxAR-ADP高于Clo+IR组(P<0.05)。Clo+IR组大鼠断尾出血时间高于IR组(P<0.05)。Clo+IR组TI、MD均低于IR组(P均<0.05),TMAO+Clo+IR组MD低于IR组(P<0.05),TMAO+Clo+IR组TI高于Clo+IR组(P<0.05)。结论Clo可以诱导血小板再生、抑制血小板聚集、延长断尾出血时间、减轻心肌血栓负荷,而TMAO可以部分抑制Clo的抗血小板聚集作用,导致Clo抵抗。Objective To observe the inhibitory effect of trimethylamine-N-oxide(TMAO)on clopidogrel(Clo)against platelet aggregation.Methods Nineteen male SD rats were randomly divided into the IR group,Clo+IR group,and TMAO+Clo+IR group.In the IR group,we made IR models.The rats in the Clo+IR group were given Clo solution intragastrically for 4 days before the IR models were made.In the TMAO+Clo+IR group,Clo solution was administered intragastrically for 4 days,and TMAO solution was injected into the tail vein before the IR models were made.Carotid venous blood was collected from rats,and platelet count,mean platelet volume(MPV)and large platelet ratio(P-LCR)were measured by automatic blood fluid analyzer.Platelet aggregation functions,including maximum aggregation rate(MaxARADP),average aggregation rate(AveAR-ADP),and maximum aggregation time(MaxAT-ADP),were measured by platelet aggregation function analyzer.The tail was severed 4 h after reperfusion and the bleeding time was observed.The myocardial thrombotic load of rats was observed by immunostaining,which was expressed by the maximum thrombotic concentration(MD)and thrombotic index(TI).Results The platelet count in the Clo+IR group was significantly higher than that in the IR group(P<0.05).Platelet MaxAR-ADP and AveAR-ADP in the Clo+IR group and TMAO+Clo+IR group were lower than those in the IR group(both P<0.05),while platelet MaxAR-ADP in the TMAO+Clo+IR group was higher than that in the Clo+IR group(P<0.05).The duration of caudal bleeding in the Clo+IR group was longer than that in the IR group(P<0.05).TI and MD in the Clo+IR group were lower than those in the IR group(both P<0.05),MD in the TMAO+Clo+IR group was lower than that in the IR group(P<0.05),and TI in the TMAO+Clo+IR group was higher than that in the Clo+IR group(P<0.05).Conclusion Clo can induce platelet regeneration,inhibit platelet aggregation,prolong the time of caudal bleeding,and reduce myocardial thrombotic load,while TMAO can partially inhibit the anti-platelet aggregation effect of Clo,leading t

关 键 词：氧化三甲胺 氯吡格雷 药物抵抗 缺血再灌注 血小板 

分 类 号：R54[医药卫生—心血管疾病]