摘要: |
【目的】 制备载rtPA的 Pluronic F127(NP-rtPA) 缓释系统,并检验超声对于其在体外血肿和在大鼠脑出血模型中血肿溶解的情况,并对其在脑出血大鼠模型术后的行为学改变情况予以评价。 方法 分为5组,即对照组、rtPA组,rtPA US组、NP-rtPA组和NP-rtPA US组,超声组选用频率1MHz,功率0.4W。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,在6小时、24小时、72小时检测血肿的溶解情况;然后制作大鼠脑出血模型,分别用rtPA和NP-rtPA注入血肿腔, 用超声(频率1MHz,功率0.4W)控制rtPA的释放,在(0d、1d、3d和7d)测定脑组织尿激酶含量、 在第7天检测脑组织含水量, 在不同的时间段内(0d、1d、3d、7d、14d、21d和28d)用改良神经功能评分(modified neurological severity score, mNSS)来检测大鼠的行为学变化;并观察脑组织病理学变化。 |
关键词: 重组组织型纤溶酶原激活剂、普朗尼克-F127、超声、血肿 |
DOI: |
投稿时间:2016-07-19修订日期:2016-10-22 |
基金项目: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) |
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Study of ultrasound activation controlled released hemolysis in vitroby the rtPA-loaded Pluronic F127 micelles |
Sun Wei,Liu wei dong |
(Punan Hospital) |
Abstract: |
Objective To prepare loading recombinant tissue type plasminogen activator (rtPA) Pluronic -F127 (NP-rtPA) delivery system, and test the ultrasound effect in vitro and in rat hematoma model of cerebral hemorrhage in vivo, in order to evaluate its neurological behavior changes. Methods We prepared a NP-rtPA delivery system,assess the use of ultrasounds(US)to dissolve hematoma in vitro using as specimens from patients with hematoma hematoma in hypertensive cerebral hemorrhage, divided into control group, rtPA group, rtPA group, ultrasound NP-rtPA group and NP-rtPA US group, respectively, in the dissolution 6 h, 24 h, 72 h detection of hematomaand in a rat model of intracerebral hemorrhage (ICH)in vivo,which divided into rtPA, rtPA US, NP-rtPAand NP-rtPA US group;and evaluate the neurological response of the ICH rat model.The hematoma dissolution in vitro was measured at 6,24,and 72 hours. Then,to create a rat model of ICH in vivo,rtPA and NP-rtPA were injected into the hematoma cavity with US-controlled release of rtPA at scheduled times. The neurological behaviors of rats were valued in 0d, 1d, 3d, 7d,14d,21d and 28d with modified neurologic severity score (mNSS). Results NP-rtPA US dissolved hematoma 40% at 6 hours and 60% at 72 hours compared with the control rtPA (dissolving 20% and 40%,respectively). There was an obvious difference at 0 and 1 day between the rtPA and Np-rtPA. The water content in brain tissue was found to be statistically different. Differences in the behavior of rats treated with rtPA US and Np-rtPA US were statistically significant at 21 and 28 days. Conclusion Ultrasound can control the release of rtPA from rtPA-Pluronic F127(NP-rtPA),making it better at dissolving hematoma,which effect was better than that that achieved with common rtPA. In addition,this treatment may reduce brain edema and provide an effective method for the removal of residual hematoma in ICH using minimally invasive surgery. |
Key words: recombinant tissue-type plasminogen activator (rtPA), Pluronic -F127, ultrasound, hematoma |