血栓靶向相变纳米粒穿透深度与其溶栓效果相关性的实验研究  

Correlation between the penetration depth and thrombolytic efficacy of phase-transitional nanoparticles in arterial thrombosis:a experimental study

作　　者：钟毅欣 叶曼[2] 徐杰[1] 张文丽 胡柳 方霓 郭大静[1] ZHONG Yixin;YE Man;XU Jie;ZHANG Wenli;HU Liu;FANG Ni;GUO Dajing(Department of Radiology,the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China)

机构地区：[1]重庆医科大学附属第二医院放射科,重庆市400010 [2]武汉大学人民医院放射科

出　　处：《临床超声医学杂志》2021年第6期401-405,共5页Journal of Clinical Ultrasound in Medicine

基　　金：中国博士后科学基金项目(2019M663891XB、2020T130761)。

摘　　要：目的探讨相变型纳米粒靶向动脉血栓穿透深度及其与体外溶栓效果的相关性。方法通过双乳化法制备一种靶向纤维蛋白的PLGA-PFH-CREKA纳米粒,验证其理化特性。采集新西兰大白兔的动脉血制作动脉血栓模型,分别加入荧光标记的PLGA-PFH-CREKA纳米粒(兔靶向PT组)、PLGA-PFH纳米粒(兔非靶向PT组)、PLGACREKA纳米粒(NPT组),应用1 W/cm2的低强度聚焦超声辐照,记录辐照前后血栓质量,计算溶栓率;使用共聚焦显微镜观察处理后的血凝块切片,测量穿透深度。应用线性回归分析血栓穿透深度与溶栓率的相关性。建立SD大鼠腹主动脉血栓模型,随机分为大鼠靶向PT组和大鼠非靶向PT组,评价其体内靶向能力。结果制备的靶向纤维蛋白的PLGAPFH-CREKA纳米粒平均粒径(297.8±11.82)nm,表面平均电位(1.44±0.22)mV,结构呈均匀球体,分散性好。体外溶栓实验显示,兔靶向PT组、兔非靶向PT组、NPT组对血栓的穿透深度分别为(293.01±24.61)μm、(114.52±23.85)μm、(116.78±28.06)μm,差异有统计学意义(F=96.187,P<0.001);兔靶向PT组与兔非靶向PT组和NPT组比较差异均有统计学意义(均P<0.001),NPT组与兔非靶向PT组比较差异无统计学意义。兔靶向PT组、兔非靶向PT组及NPT组靶向溶栓率分别为(60.67±4.37)%、(45.83±6.88)%、(18.67±1.78)%,差异有统计学意义(F=108.508,P<0.001);组间两两比较差异均有统计学意义(均P<0.001)。线性回归分析显示兔靶向PT组对血栓穿透深度与溶栓率呈正相关(R^(2)=0.818,P<0.05)。体内靶向能力实验显示,大鼠靶向PT组对血栓的靶向性较大鼠非靶向PT组更好。结论成功制备了靶向纤维蛋白的PLGAPFH-CREKA纳米粒,其对血栓纤维蛋白有良好的靶向性,溶栓效果较好,对血栓穿透性佳,且相变所致溶栓率与血栓穿透深度呈正相关。Objective To investigate the correlation between the penetration depth and thrombolytic efficacy of phasetransitional(PT)nanoparticles(NPs)in arterial thrombosis.Methods Fibrin targeted PLGA-PFH-CREKA NPs was developed by double emulsification method,and its physical and chemical properties were verified.The preparation of arterial thrombosis was acquired through the New Zealand white rabbit,then the thrombi were collected in the PLGA-PFH-CREKA NPs(rabbit targeted PT group),PLGA-PFH NPs(rabbit non-targeted group)and PLGA-CREKA NPs(NPT group)respectively,LIFU with sound power density of 1 W/cm2 was used to irradiate outside.The quality of thrombi was recorded before and after the experiment,the thrombolytic rate was calculated,and frozen sections of blood clot were used to measure penetration depth by confocal microscope.The correlation between thrombolytic rate and the penetration depth of NPs was analyzed by Linear regression analysis.Then the abdominal aortic thrombosis model was established in SD rats,and randomly divided into rat targeted PT group and rat non-targeted PT group to evaluate the targeting ability in vivo.Results The fibrin-targeted PT NPs were successfully prepared with a particle of(297.8±11.82)nm and a surface Zeta potential of(1.44±0.22)mV,the NPs also have a uniform spherical structure with good dispersibility.Thrombolytic assay in vitro showed that the penetration depth of thrombus in rabbit targeted PT group,rabbit non-targeted PT group and NPT group were(293.01±24.61)μm,(114.52±23.85)μm and(116.78±28.06)μm,respectively,and the difference was statistically significant(F=96.187,P<0.001).There were statistically significant differences between the rabbit targeted PT group,the rabbit non-targeted PT group and NPT group(all P<0.001),while there was no statistically significant difference between the NPT group and the rabbit non-targeted PT group.In addition,the thrombolysis rate of the rabbit targeted PT group,the non-targeted PT group and the NPT group were(60.67±4.37)%,(45.83±6.88)

关 键 词：相变纳米粒 靶向 动脉血栓 溶栓率 穿透性 相关性 

分 类 号：R445.1[医药卫生—影像医学与核医学]