脂质体携载前列腺素E_1抑制血小板功能降低心肌梗死面积

Effects of liposomal prostaglandin E_1 on the inhibition of platelet function and the limition of myocardial infarct size

目的 在家兔心肌缺血 再灌注模型上观察脂质体携载前列腺素E1(Lipo PGE1)对血小板功能的抑制作用和对缺血心肌的保护作用。方法 2 0只家兔随机分成Lipo PGE1治疗组及对照组 ,每组 10只。两组家兔左冠状动脉前降支结扎 4 0min后松开 ,再灌注 2h。于再灌注前 10min分别自耳缘静脉注射Lipo PGE1( 2 μg/kgPGE1)及等容量的脂肪乳剂 (Lipo PGE1的溶剂 )。整个实验过程中连续记录血压及心电变化。家兔处死后以Evans蓝及氯化三苯基四氮唑 (TTC)双重染色确定缺血及梗死心肌范围 ,心肌梗死范围以梗死心肌占危险区心肌重量百分比 (MI/RISK)表示。通过测定血浆血栓素B2 (TXB2 )及α颗粒膜蛋白 14 0 (GMP 14 0 )含量反映周围血小板活性状态。结果 再灌注前静脉应用 2 μg/kgLipo PGE1能减少家兔再灌注期心律失常的发生 ,不产生明显的血流动力学障碍。Lipo PGE1治疗组心肌梗死范围 ( 3 3 .6± 5 .5 ) %较对照组 ( 4 3 .8± 5 .1) %显著缩小 (P <0 .0 1)。Lipo PGE1治疗组再灌注期血浆TXB2 及GMP 14 0含量较对照组明显降低 (P <0 .0 5及P <0 .0 1) ,血小板最大聚集率较对照组也明显降低 (P <0 .0 1)。结论 Lipo PGE1能显著抑制血小板聚集、活化 ,挽救缺血心肌 ,缩小心肌梗死范围。

Objective To determine the effects of liposomal prostaglandin E 1(Lipo-PGE 1)on platelet function and infarct salvage in a rabbit ischemia-reperfusion model. Methods Twenty open-chest rabbits were randomized to receive a 10-minute intravenous infusion of either liposome diluent(placebo)or Lipo-PGE 1 (2 μg/kg PGE 1 )after 40 minutes of left anterior desending (LAD) ligation ,which infusions started 10 minutes just before reperfusion. Carotid arterial pressure and electrocardiogram were monitored and recorded continuously throughout the whole experiment. After 2 hours reperfusion, infarct size and risk region were measured by postmortem dual dyes with triphenyl tetrazolium chloride (TTC) and Evans blue. Platelet activation detection was performed by plasma thromboxane B 2 (TXB 2 ) and alphagranule membrane protein (GMP-140). Ex vivo platelet aggregation reported as the maximal percentage was studied before and 10 minutes after the administration of Lipo-PGE 1 or placebo. Results There was a dramatic reduction of arrhythmias during reperfusion in treatment group with Lipo-PGE 1 than in control group. Infarct size as a ratio of weight of infarcted tissue to weight of risk region (MI/RISK) was significantly reduced with Lipo-PGE 1 (33.63±5.50)% compared with placebo(43.79±5.14)% infusion (P<0.01). The values of plasma TXB 2 and GMP-140 from multiple blood samples obtained during reperfusion in treatment of Lipo-PGE 1 group were significantly reduced than in control group (P<0.05 or P<0.01). There was a dramatic reduction of platelet aggregation after treatment with Lipo-PGE 1 than before treatment(66.08% versus 52.61%, P<0.05).Conclusion Lipo-PGE 1 can effectively inhibit platelet aggregation and activation, and limit myocardial infarct size.