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研究评价了豆豉纤溶酶(Subtilisin FS33)RGDS-载酶脂质纳米粒的溶栓效果和靶向性,探讨RGDS-脂质体作为载体导向于血栓灶的可能性。不同剂量荧光标记RGDS-载酶脂质体给予血栓模型动物,考察其对机体抗凝血和纤溶功能的影响,以及组织器官的荧光素分布,结果发现,Subtilisin FS33高剂量组注射15 min～2 h,机体的APTT、PT和TT都明显延长(P<0.05,P<0.01),纤溶酶活力明显增高(P<0.05),血浆FDP的含量升高(P<0.05,P<0.01),D-di mer均呈阳性,ELT值降低;低剂量组也有相似趋势(P<0.05);RGDS-载酶脂质体组的大鼠组织切片中脑静脉和肾小球毛细血管中无明显血栓,只有少量红细胞聚积,并且在脑、心脏和肝组织中荧光物的含量显著高于无RGDS-载血清白蛋白脂质体组(空白对照组)。试验表明静注RGDS-载酶脂质体可明显增强机体的抗凝和纤溶能力,RGDS-载酶脂质体具有一定的血栓靶向性。
This study evaluated the thrombolytic effect and targeting of RGDS-loaded liposome nanoparticles of Subtilisin FS33 and explored the possibility of targeting RGDS-liposomes as a carrier to the thrombosis foci. The effects of different doses of fluorescent labeled RGDS-lipase on thrombus model animals were investigated, and their effects on anticoagulant and fibrinolytic function and the distribution of fluorescein in tissues and organs were investigated. The results showed that Subtilisin FS33 high- (P <0.05, P <0.01), the plasmin activity was significantly increased (P <0.05) and the content of plasma FDP was increased (P <0.05, P <0.01) , D-di mer were positive, ELT value decreased; low-dose group also have a similar trend (P <0.05); RGDS-containing liposomes in rat tissue sections in the brain vein and glomerular capillary no significant Thrombosis, only a small amount of erythrocyte accumulation, and in the brain, heart and liver fluorescence content was significantly higher than without RGDS-serum albumin liposome group (blank control group). Experiments show that intravenous injection of RGDS-containing lipase can significantly enhance the body’s ability to anticoagulant and fibrinolytic, RGDS-containing liposomes have some thrombus targeting.