尿激酶脂质体对犬冠状动脉内血栓的加速溶栓作用

Accelerated thrombolysis by liposomal-encapsulatedurokinase in a canine model of acute myocardialinfarction

用之污剂清除技术制备尿激酶脂质体（ＬＥＵＫ），尿激酶（ＵＫ）包裹率２５．６％。ＬＥＵＫ直径６０．４±１３．６ｎｍ，属中性大单层脂质体。在４℃缓冲液中贮存４８ｈ，ＵＫ渗漏率７．ｌ％。ＬＥＵＫ、ＵＫ在３７℃少含血小板血浆中孵化相同时间，ＬＥＵＫ组剩余ＵＫ活性百分率显著高于ＵＫ组（３０分钟为：８４．３±３Ｄ％，４６±４％；６０分钟为６０±５％，１４．９±０．８％。Ｐ＜０．０１）。提示脂质体能保护ＵＫ的纤溶能力，ＬＥＵＫ较ＵＫ半衰期延长一倍多。用凝血酶形成血栓后阻断动脉，建立犬急性冠状动脉内血栓模型，与ＵＫ进行溶栓对照研究（ｎ＝５）。结果ＬＥＵＫ组血管再通时间（２８±７ｍｉｎ）较ＵＫ组（６９±７ｍｉｎ，Ｐ＜０．０ｌ）缩短一倍多。剂量相应减小。溶栓后血中剩余纤维蛋白原ＬＥＵＫ织（２．５±０．５ｇ／Ｌ）显著高于ＵＫ组（１６±０．４，Ｐ＜００ｌ）。表明ＬＥＵＫ对加速溶栓减少出血并发症有实用价值。

e prepared liposomal-encapsulated urokinases(LEUK) by detergent removal technique. Theencapsulated efficiency of urokinase (UK) was 25.6% .The LEUKs were neutral large unilamellar vesiclesand its average diameter was 60.4±13.6 nm underelectron microscope. Measurements of UK activity in-dicated about 7.1% loss of activity or leakage intris-buffered saline over a 48 hr period at a tempera-ture of 4℃ . After the same time incubation of LEUKand UK in human platelet -poor plasma (PPP) at37℃, the pereentage of UK activity in LEUK groupwas remaining higher than that of UK group (30min:84.3 ±3.0% to 46± 4%; 60 min: 60±5% to 14.9 ±0.8%, P<0.0l). These results suggest that liposomespreserve the thrombolytic potential of UK and thatthe haif-life of UK in liposomes prolonges more thantwo times. Canine model of acute myocardialinfaretion was based on a thrombos obstruction.Thrombolysis tests were compared for LEUK and UK(n = 5). The time for restoring vessel patency redueedmore than 50% when compared with that in UKgroup (28 ±7 min to 69 ± 7 min, P<0.0l). The totaldosage of LEUK was correspondingly lower. Afterone-hour thrombolysis, the fibrinogen of LEUKgroup (g / L) was considerably higher than that of UKgroup (2.5 ± 0.5 to 1.6 ± 0.4, P<0.0l). These resultssuggested that LEUK may be of practical significancein accelerating thrombolysis and reduction in bleedingcomplications.