尿激酶热敏脂质体的体内溶栓实验

目的观察以二棕榈酸磷脂酰胆碱和尿激酶(UK)为原料制备的UK热敏脂质体对兔颈总动脉血栓的溶栓效果。方法采用反相蒸发法制备UK热敏脂质体并测定其包封率;新西兰大白兔24只随机分为对照组(输PBS液)、15万U/kg UK组、5万U/kg UK热敏脂质体组、7.5万U/kg UK热敏脂质体组,每组6只;FeCl3包裹兔颈总动脉,建立血栓模型;颈动脉压降至最低点时,分别给4组输入不同药物,记录血压动态变化;最后取各组血栓段血管和心、肝、脾、肺、肾做病理学检查。结果所制备的UK热敏脂质体包封率为65%,脂质体呈圆形或椭圆形,直径为0.08-0.36μm;7.5万U/kg UK热敏脂质体组与15万U/kg UK组比较溶栓效果相似,但前者UK用量仅为后者的1/2,且各脏器均未见出血。结论UK热敏脂质体在溶栓治疗中有良好的靶向性,且出血副作用小。如能进一步优化,可为临床的溶栓治疗提供一条新途径。

Preparation of urokinase temperature-sensitive liposome and its in vivo thrombolytic experiment

Objective To prepare temperature-sensitive liposome composed of dipalmitoyl phosphatidylcholine(DPPC) and urokinase(UK) and observe its thrombolytic efficacy in thrombosis model of rabbits.Methods Reverse phase evaporation method was used to formulate the liposome and its entrapment efficiency was detected.Experimental animals were divided into 4 different groups:control group,15×104 U/kg UK group,5×104 U/kg UK temperature-sensitive liposome group and 7.5×104 U/kg UK temperature-sensitive liposome group.The thrombosis model of common carotid artery was established by wrapping the artery with ferric chloride.When the blood pressure fell to the lowest point,drugs were injected to 4 different groups and change of blood pressure was observed.Histopathologic changes of thrombotic blood vessels and heart,liver,spleen,lung and kidney were examined respectively in different groups.Results Entrapment efficiency of the liposome was 65%,which was round or elliptic and the diameter was 0.08～0.36 μm.The group of 7.5×104 U/kg UK temperature-sensitive liposome and the group of 15×104 U/kg UK were similar in thrombolytic effect,but the UK dose of the former was 1/2 of the latter and there was no hemorrhage in the former.Conclusion UK temerature-sensitive liposome has targeting effect in thrombolytic therapy and the side-effect of hemorrhage is minimal.It may offer an available means for therapy of clinical thrombosis if it can be improved in the future.