脂质体携载前列腺素E_1抗心肌缺血再灌注损伤

目的　研究脂质体携载前列腺素E1(Lipo PGE1)减轻心肌再灌注损伤的机理。方法　 2 4只家兔随机分成Lipo PGE1组 ,PGE1组及对照组 ,每组 8只。以家兔左冠脉前降支 (LAD)结扎 6 0min ,再灌注 12 0min为缺血再灌注模型 ,于再灌注前 10min分别自耳缘静脉静注Lipo PGE1(2 μg·kg-1PGE1) ,PGE1(2 μg·kg-1)及等容量的脂肪乳剂 (Lipo PGE1的溶剂 ) ,以Evans蓝及氯化三苯基四氮唑 (TTC)双重染色确定缺血心肌及梗塞心肌范围 ,通过测定心肌组织髓过氧化物酶 (MPO)活性反应缺血心肌中性粒细胞浸润程度。结果　Lipo PGE1组梗塞心肌占危险区心肌重量百分比(32 2 0 %± 4 70 % )比较对照组 (44 5 7%± 5 46 % )及PGE1(42 0 9%± 6 93% )降低 (P <0 0 1) ;Lipo PGE1治疗组缺血区心肌组织MPO活性〔(1 9± 1 2 )U·g-1〕较对照组〔(5 3± 2 4)U·g-1〕及PGE1组〔(4 2± 2 0 )U·g-1〕均降低 ,边缘区心肌组织MPO活性〔(1 4± 1 1)U·g-1〕较对照组〔(3 3± 1 5 )U·g-1〕也降低 (P <0 0 5 )。结论　Lipo PGE1能有效抑制再灌注心肌中性粒细胞的浸润 ,减轻心肌再灌注损伤。

Effects of liposomal prostaglandin E1 against myocardial reperfusion injury in rabbits

AIM To test the hypothesis that intravenous liposomal prostaglandin E 1 (Lipo PGE 1) would attenuate reperfusion injury in a rabbit ischemia reperfusion model. METHODS Twenty four open chest rabbits were randomized to receive a 10 minute intravenous infusion of either liposome diluent (placebo), free PGE 1 (2 μg·kg -1 ), or Lipo PGE 1(2 μg·kg -1 PGE 1) after 60 minutes of left anterior desending (LAD) ligation just before reperfusion. Carotid arterial pressure and electrocardiogram were monitored and recorded continously throughout the whole experiment. After 2 hours reperfusion, infarct size and region at risk were measured by postmortem dual dyes with triphenyl tetrazolium chloride (TTC) and Evans blue. Myocardial leukocyte infiltration by myeloperoxidase (MPO) assay was performed. RESULTS Infarct size as a ratio of weight of infarcted tissue to weight of region at risk (MI/RISK) was significantly reduced with Lipo PGE 1 32.20%±4.70% compared with PGE 1 42.09%±6.93% or placebo 44.57%±5.46% ( P <0 01) infusion. There was a dramatic reduction in myeloperoxidase activity in the ischemia and border regions of rabbits treated with Lipo PGE 1 compared with placebo ( P <0 01 or P <0 05). Enzyme activity was also significantly reduced ( P <0 05) in the ischemia zone with Lipo PGE 1 〔(1 9±1 2) U·g -1 〕 treatment compared with PGE 1〔(4 2±2 0) U·g -1 〕. CONCLUSION Lipo PGE 1 can effectively inhibit neutrophil infiltration, attenuate reperfusion injury, limit myocardial infarct size without adverse hemodynamic consequences.