超声控释载rtPA的普朗尼克-F127控释给药系统对脑内血肿促溶的实验研究  

Study on hemolysis by ultrasound activated controlled release of rtPA-loaded Pluronic F127 micelles

作　　者：孙伟[1] 段友容[2] 钱忠心[1] 刘卫东[1] 

机构地区：[1]上海市浦东新区浦南医院神经外科,200125 [2]上海市肿瘤研究所国家重点肿瘤基因研究室

出　　处：《临床超声医学杂志》2016年第11期756-760,共5页Journal of Clinical Ultrasound in Medicine

基　　金：上海市浦东新区科委项目(PKJ2012-Y58;PKJ2015-Y25);上海市浦东新区卫生系统优秀青年医学人才培养(PWRq2013-13)

摘　　要：目的制备载重组组织型纤溶酶原激活剂(rt PA)的普朗尼克-F127(NP-rt PA)控释给药系统,并检验超声对其在人体外血肿和大鼠脑出血模型中血肿溶解的情况,评价大鼠脑出血模型术后的行为学改变情况。方法人体外血肿溶解实验采用高血压性脑出血患者的血肿块作为标本,分为对照组、rt PA组、rt PA+US组、NP-rt PA组及NP-rt PA+US组,分别在6 h、24 h、72 h检测血肿的溶解情况。建立大鼠脑出血模型,分为假手术组、阴性对照组、rt PA组、rt PA+US组、NP-rt PA组及NP-rt PA+US组,在0 d、1 d、3 d及7 d测定体内rt PA浓度,在7 d测定脑组织含水量,在0 d、1 d、3 d、7 d、14 d、21 d及28 d采用改良神经功能评分(m NSS)评价大鼠行为学变化,并观察脑组织病理学变化。结果人体外血肿溶解实验中NP-rt PA+US组在6 h、24 h及72 h的血肿溶解率分别与rt PA组、rt PA+US组及NP-rt PA组比较,差异均有统计学意义(均P<0.05)。大鼠脑出血中血肿溶解实验中,NP-rt PA+US组在0 d和1 d体内rt PA浓度与rt PA+US组比较,差异均有统计学意义(均P<0.05);且NP-rt PA+US组在1d、3d及7d体内rt PA浓度比较,差异均有统计学意义(均P<0.05)。NP-rt PA+US组脑组织含水量最低,与阴性对照组和rt PA+US组比较,差异均有统计学意义(均P<0.05)。阴性对照组在21 d和28 d的m NSS评分与rt PA+US组和NP-rt PA+US组比较,差异均有统计学意义(均P<0.05)。结论超声能控制NP-rt PA控释给药系统释放rt PA,使其更好地溶解血肿,较单纯rt PA溶解效果更好,可以更好地减轻动物体内的脑水肿,为高血压性脑出血的微侵袭外科治疗提供了一种有效的清除残余血肿的方法。Objective To prepare Pluronic-F127 delivery system loaded with recombinant tissue type plasminogen activator（rt PA）（NP-rt PA）,and detect the effect of ultrasound on hemolysis in vitro and in rat hematoma model of cerebral hemorrhage in vivo,and to evaluate the neurological behavior changes after establishment of rat cerebral hemorrhage model.Methods NP-rt PA delivery system was prepared,the effect of ultrasound in dissolving the hematoma in vitro was assessed by using hematoma specimens from the patients with hypertensive cerebral hemorrhage. The hematomas were divided into control group,rt PA group,rt PA ＋US group,NP-rt PA group and NP-rt PA ＋US group,respectively. The dissolution of the hematoma was detected 6 h,24 h and 72 h after the treatment. A rat model of intracerebral hemorrhage（ICH）in vivo was established,the rats were divided into false operation group,negative control group,rt PA,rt PA ＋US,NP-rt PA and NP-rt PA ＋US group. The rt PA concentration were measured on 0 d,1 d,3 d and 7 d. The brain water content were measured on 7 d.The neurological behaviors of rats were evaluated on 0 d,1 d,3 d,7 d,14 d,21 d and 28 d with modified neurologic severity score（m NSS）. Results In vitro experiment,there was significant difference of dissolution rate of the hematoma between NP-rt PA ＋US group and rt PA,rt PA ＋US and NP-rt PA group on 6 h,24 h and 72 h（P〈0.05）. In vivo experiment,there was significant difference of rt PA concentration between NP- rt PA ＋ US group and rt PA ＋ US group on 0 d,1 d（P〈0.05）.In NP-rt PA＋US group,the rt PA concentration had significant difference on 1 d,3 d and 7 d（P〈0.05）. The water content in brain tissue was found to be statistically different.

关 键 词：重组组织型纤溶酶原激活剂 普朗尼克-F127 超声 血肿 大鼠 

分 类 号：R722.15[医药卫生—儿科] R445.1[医药卫生—临床医学]