前列腺素E1对兔动脉粥样硬化易损斑块的影响

Effect of Prostaglandin E1 on Vulnerable Plaque in Rabbits

目的研究前列腺素E1对兔动脉粥样硬化易损斑块的影响及机制。方法 22只新西兰大白兔高脂饲料(1%胆固醇)喂养2周后,进行腹主动脉球囊损伤术,术后继续高脂喂养,7周后,随机分为模型组、前列腺素E1组和辛伐他汀组,同时改为普通饲料继续喂养4周,13周末,所有兔给予中国斑点蝰蛇毒和组胺进行药物诱发。观察药物干预后血脂、斑块形态、斑块组分及炎症因子的变化。结果前列腺素E1对血脂没有影响;与模型组比较,前列腺素E1组能显著增加斑块的纤维帽厚度(101.72±34.89μm比79.86±16.98μm,P<0.01),减小斑块易损指数(0.94±0.27比3.83±1.45,P<0.01);并且能够显著抑制斑块中巨噬细胞的累积(P<0.01)及其分泌的炎症因子基质金属蛋白酶1和基质金属蛋白酶9的表达(P<0.01),前列腺素E1组与辛伐他汀组比较差异无显著性。结论前列腺素E1能够稳定兔动脉粥样硬化易损斑块,该作用与脂质代谢无关,但与抑制斑块中巨噬细胞的累积及其分泌炎症因子密切相关。

Aim To investigate the effect and mechanism of prostaglandin E1 on atherosclerotic vulnerable plaque in rabbits. Methods 22 rabbits were fed a 1% cholesterol diet 2 weeks prior to and 7 weeks after balloon injury of the abdominal aorta.Thereafter the atherogenic diet was replaced with a regular diet,and rabbits were randomly divided into 3 groups for 4 weeks＇ treatment： control group,prostaglandin E1 group and simvastatin group.At the end of week 13,all rabbits were challenged with injection of Chinese Russell＇s viper venom and histamine.Serum,plaque morphology,plaue composition and inflamatory expression studies were performed. Results Prostaglandin E1 did not alter serum lipid levels.Prostaglandin E1 significantly increased the thickness of the fibrous caps（101.72±34.89 μm vs 79.86±16.98 μm,P0.01） and decreased plaque vulnerability index（0.94±0.27 vs 3.83±1.45,P0.01）;Prostaglandin E1 attenuated macrophage accumulation（P0.01） and MMP-1,MMP-9 expression（both P0.01） within the plaque,and there was no statistical difference between prostaglandin E1 group and simvastatin group. Conclusion Prostaglandin E1 effectively enhanced stability of vulnerable plaque in rabbit model independent of serum lipid levels,in which inhibiting macrophage accumulation and inflammatory expression within plaque may play an important role.