Kritz H, Sinzinger H, Lupattelli G, Virgolini I, Fitscha P, O'Grady J
Wilhelm Auerswald Atherosclerosis Research Group (ASF) Vienna, Austria.
Eur J Clin Pharmacol. 1997;52(3):191-7. doi: 10.1007/s002280050273.
An increased apo B-containing lipoprotein influx and cholesterol ester accumulation in arteries are well-known events in human atherogenesis. In vitro and experimental animal studies have provided evidence of a beneficial effect of PGE1 on both vascular apo B-containing lipoprotein accumulation and cholesterol ester content.
We examined the effect of PGE1 (administered via an intravenous portable infusion pump at a rate of 5 ng PGE1 kg-1.min-1 for 5 days a week, 6 h daily, over a total of 5 weeks) in ten patients (eight males, two females) on 123I-apo B-containing lipoprotein accumulation into the large arteries in vivo. Apo B-containing lipoprotein isolation was carried out by immunoaffinity chromatography and radiolabeling with the iodine monochloride method. 123I-apo B-containing lipoprotein accumulation was imaged and quantified by means of special computer software before and after 5 weeks of PGE1 therapy.
PGE1 led to a significant decrease in maximal arterial apo B-containing lipoprotein retention. The mean decrease in the carotid and femoral arteries in type I lesions amounted to between 16.9% and 30.4%, and in type II lesions between 22.4% and 30.7%, 20 h after injection of radiolabeled apo B-containing lipoprotein. The type of arterial apo B-containing lipoprotein kinetic curves, however, remained unchanged.
These findings indicate that PGE1 decreases the apo B-containing lipoprotein influx in the large arteries and the vascular cholesterol content, suggesting that PGE1 may lead to regression of lipid-rich lesions in human in vivo.
动脉中含载脂蛋白B的脂蛋白流入增加以及胆固醇酯蓄积是人类动脉粥样硬化形成过程中众所周知的现象。体外和实验动物研究已证实前列腺素E1(PGE1)对血管中含载脂蛋白B的脂蛋白蓄积和胆固醇酯含量具有有益作用。
我们对10例患者(8例男性,2例女性)进行研究,通过静脉便携式输液泵以5 ng PGE1·kg-1·min-1的速率给药,每周5天,每天6小时,共持续5周,观察PGE1对体内123I标记的含载脂蛋白B的脂蛋白在大动脉中蓄积的影响。通过免疫亲和色谱法分离含载脂蛋白B的脂蛋白,并采用一氯化碘法进行放射性标记。在PGE1治疗5周前后,借助特殊计算机软件对123I标记的含载脂蛋白B的脂蛋白蓄积情况进行成像和定量分析。
PGE1导致动脉中含载脂蛋白B的脂蛋白最大保留量显著降低。注射放射性标记的含载脂蛋白B的脂蛋白20小时后,I型病变的颈动脉和股动脉中平均降低幅度在16.9%至30.4%之间,II型病变在22.4%至30.7%之间。然而,动脉中含载脂蛋白B的脂蛋白动力学曲线类型保持不变。
这些发现表明,PGE1可减少大动脉中含载脂蛋白B的脂蛋白流入以及血管胆固醇含量,提示PGE1可能导致人体体内富含脂质病变的消退。