^(99)Tc^m示踪血栓技术在家兔脑卒中模型的应用  

Application of ^(99)Tc^m tracer technique in rabbit cerebral thromboembolic stroke

作　　者：郝春华[1] 徐向伟[1] 马寅仲 张蕊[1] 孙双勇[1] 王维亭[1] 赵专友[1] 汤立达[1] 

机构地区：[1]天津药物研究院新药评价有限公司,天津300193

出　　处：《药物评价研究》2017年第5期648-651,共4页Drug Evaluation Research

摘　　要：目的研究同位素^(99)Tc^m示踪血栓技术在家兔脑卒中模型上的应用,并动态示踪观察重组组织型纤溶酶原激活剂(rt-PA)对血栓的溶解效果。方法将新鲜洗脱的放射性高锝酸钠(5 m Ci/2 mL,92.5 MBq/mL)0.5 mL与5 mg/mL氯化亚锡30μL充分混合成示踪标记液;分别向全血、红细胞、血浆中加入20μL示踪标记液进行同位素标记,加入50μL CaCl_2(0.5 mol/L)与牛凝血酶(50 IU/mL)混合物,迅速吸入聚乙烯塑料管(PE80)中,37℃固化2 h后取出血栓,分割成10 mm的示踪血栓,并计算标记率。采用经兔颈外动脉逆向颈内动脉插管方法,注射示踪血栓栓塞大脑中动脉,制备脑卒中模型,用γ计数仪在兔头部测定放射性强度即每分钟计数(Counts Per Minute,CPM)的动态变化,并观察临床等效剂量工具药rt-PA4.5 mg/kg的溶栓效果。结果全血血栓标记率为53.5%,红细胞与血浆标记比率为4.5∶1,家兔大脑中动脉血栓栓塞后CPM明显增加,约为本底的5.1±1.3倍,表明模型制备成功,检测可靠。静脉给予工具药rt-PA能产生显著的渐进性溶栓效果。结论锝标记主要以标记红细胞为主,对血浆及纤维蛋白原影响较小。^(99)Tc^m示踪血栓技术制备的脑卒中模型,分离区明显,模型制备成功、指标检测科学,模型对药物疗效应答能力的反应稳定、可靠。Objective To study the application of ^99Tc^m in rabbit cerebral thromboembolic stroke and thrombolysis effect of recombinant tissue plasminogen activator （rt-PA）.Methods The 0.5 mL radioactive pertechnetate sodium （specification：5 mCi/2mL and radiation intensity 92.5 MBq/mL） was combined with 30 μL stannous chloride （5 mg/mL）,and the 20 μL mixture was joined to whole blood,red blood cells,and plasma for labelling.Then 50 μL CaCl2 （0.5 mol/L） and bovine thrombin （50 IU/mL） were doped in mixture,and rapidly sucked into a polyethylene plastic pipe （PE80）.Thrombus was formed for 2 h at 37 ℃ and cut into small pieces of 10 mm.Autologous blood clots combined with ^99Tc^m from external carotid artery were injected to internal carotid artery of rabbit,the radioactivity （counts per minute,CPM） was measured by gamma counting instrument,and the improvement of rt-PA 4.5 mg/kg （clinical equivalent dose） on this model was observed.Results After thromboembolism,CPM increased approximately by （5.1 ＆#177; 1.3） times,which suggested that the model was reliable.The rt-PA 4.5 mg/kg had significant progressive thrombolysis effect.Conclusion ^99Tc^m tracer technology could be applied to rabbit cerebral stroke model,which is stable and reliable

关 键 词：^99TC^M 家兔 脑卒中 RT-PA 溶栓 

分 类 号：R965.2[医药卫生—药理学]