摘要目的 制备可释氧的载过氧化氢(H2 O2 )相变纳米粒,联合低强度聚焦超声(LIFU )靶向溶解人工血管内血栓,探讨其在急性心肌梗死(AMI)冠状动脉溶栓治疗中的价值.方法 采用薄膜水化和双乳化法制备包载 H2 O2 和液态氟碳(PFP)的脂质相变型纳米粒.取家兔颈总动脉血50 ml制备成质量约400～800 mg的血栓块.本实验分为4组: PBS对照组(A组) 、 SonoVue微泡组(B组) 、PFP相变纳米粒组(C组)和载H2 O2 相变纳米粒组(D组) .每组血栓样本均置入体外溶栓模拟循环装置的人工血管中联合LIFU辐照.称量各组溶栓前后血栓重量并观察比较各组溶栓后 HE染色切片;溶氧仪检测溶栓后循环液中纳米粒释氧量.结果 载 H2 O2 相变纳米粒粒径大小为(456 .7 ± 31 .2 ) nm ;荧光显微镜示纳米粒液体相时结构稳定,大小均一.溶栓后四组血栓重量损失及损失率分别为 A 组(52 .2 ± 11 .5) mg 、 (9 .7 ± 3 .5 )%, B组(110 .0 ± 21 .9 ) mg 、 (19 .4 ± 2 .4 )%, C组(239 .6 ± 46 .3 ) mg 、 (39 .7 ± 6 .3)%, D组(309 .8 ± 44 .8) mg 、 (54 .2 ± 6 .6)%, C组和D组溶栓前后的重量损失及损失率明显大于A、B两组,差异有统计学意义(均 P ＜0 .01);C组、D组间差异无统计学意义( P ＞0 .05) .溶氧仪检测纳米粒释氧量随着 H2 O2 浓度的增加而逐渐增高.结论 载 H2 O2 相变纳米粒可高效溶解人工血管血栓栓塞,并通过释氧改善组织缺氧,为 AM I患者冠状动脉血栓栓塞提供潜在的治疗新方式.

abstractsTo prepare a novel H2 O2‐loaded and phase‐change nanoparticles ,combined with low intensity focused ultrasound ( LIFU ) to dissolve intravascular thrombosis for the evaluation of its value in the treatment of coronary artery thrombolysis in the patients with acute myocardial infarction ( AM I) . Methods H2 O2‐loaded and phase‐change nanoparticles were prepared by membrane hydration method . 50 ml arterial blood was collected from rabbit carotid artery and made into 400－800 mg thrombus blocks . T hey were divided into four groups randomly :poly butylene succinate buffer ( PBS ) solution as blank control ( group A ) ,SonoVue microbubbles group ( group B) ,PFP phase‐change nanoparticles group ( group C ) , H2 O2‐loaded and phase‐change nanoparticles group ( group D ) . Each group of thrombus samples were placed into the artificial blood vessels of the extracorporeal thrombolysis simulation cycle device and combined with LIFU irradiation . T he weights and pathological presentations were compared before and after thrombolysis . T he volume of O 2 in the vascular system was inspected using Dissolved Oxygen Detector ( DOD ) after LIFU exposure . Results T he average size of H2 O2‐loaded nano‐droplets was ( 456 .7 ± 31 .2) nm . Fluorescence microscopy showed that the structure of nanoparticles was stable and uniform in size . T he weight loss and rates of thrombus in the four groups after thrombolysis were :group A ( 52 .2 ± 11 .5) mg ,( 9 .7 ± 3 .5)% ;group B ( 110 .0 ± 21 .9) mg ,( 19 .4 ± 2 .4)% ;group C ( 239 .6 ± 46 .3) mg , ( 39 .7 ± 6 .3)% and group D ( 309 .8 ± 44 .8) mg ,( 54 .2 ± 6 .6)% ,respectively . T he weight loss and rates of thrombus in group C and D were higher than those in group A and B ( all P ＜ 0 .01 ) ,but there was no significant difference between group C and D ( P ＞0 .05) . T he DOD showed that along with the increase of H2 O2 concentration ,O 2 release was rising . Conclusions H2 O2/PFP nanoparticles with LIFU performs efficient thrombolysis and provides O 2 to improve hypoxia ,w hich provides a potential novel treatment method for AM I patients with coronary embolism .