[1]刘圣,施海彬,张鹏,等.重组葡激酶动脉内溶栓治疗犬急性脑梗死的量效研究[J].介入放射学杂志,2007,(03):189.
 LIU Sheng,SHI Hai-bin,ZHANG Peng,et al.Dose-effective investigation of intraarterial r-Sak in canine model with acute cerebral infarctions[J].journal interventional radiology,2007,(03):189.
点击复制

重组葡激酶动脉内溶栓治疗犬急性脑梗死的量效研究 ()

PDF下载中关闭

分享到:

《介入放射学杂志》[ISSN:1008-794X/CN:31-1796/R]

卷:
期数:
2007年03期
页码:
189
栏目:
实验研究
出版日期:
2007-03-15

文章信息/Info

Title:
Dose-effective investigation of intraarterial r-Sak in canine model with acute cerebral infarctions
作者:
刘圣施海彬张鹏王成虎周春高李麟荪
210029南京医科大学第一附属医院放射科
Author(s):
LIU ShengSHI Hai-binZHANG PengWANG Cheng-huZHOU Chun-gaoLI Lin-sun.
Radiologic Department,The1st Affiliated Hospital,Nanjing Medical University,Nanjing210029,China
关键词:
脑梗死重组葡激酶动脉溶栓凝血纤溶
分类号:
R743.33
文献标志码:
A
摘要:
目的比较动脉内注射不同剂量重组葡激酶(r-Sak)溶栓治疗犬急性脑梗死的疗效和并发症,以探讨其相对合理的治疗剂量。方法成年比格犬24条,用介入技术建立犬脑栓塞动物模型,随机分为对照组(生理盐水10ml)、小剂量组(r-Sak5000u/kg)、中剂量组(r-Sak10000u/kg)和大剂量组(r-Sak20000u/kg)。栓塞后5h行脑血管造影观察所栓塞血管的通畅情况,插管至左颈内动脉分别在30min内注入药物行溶栓治疗,在溶栓后0.5、1及2h复查DSA,观察栓塞血管的再通情况,并分别在溶栓前0.5h、溶栓后0.5h、1h及2h抽取犬静脉血检测PT、APTT和D-二聚体。24h后处死动物行病理检查。结果溶栓后2h内造影显示对照组、r-Sak小剂量、中剂量和大剂量组的有效率分别为10.0%(1/10)、40.0%(4/10)、90.9%(10/11)和100%(9/9),各组间比较有显著性差异(P<0.001);完全通畅的比率分别为0、10%(1/10)、36.4%(4/11)、66.7%(6/9),也有统计学差异(P=0.005)。溶栓后PT、APTT在r-Sak各剂量组均显著延长(P<0.001);各组的D-二聚体在溶栓前后没有明显变化(各组P>0.05)。溶栓后r-Sak大剂量组有1例死亡,病理检查在其顶叶脑实质见出血灶,其余动物均存活。结论①在犬脑梗死的超急性期,r-Sak动脉内溶栓治疗有效、可行,r-Sak对含少量血小板的白色血栓有显著溶栓作用,剂量大或等于10000u/kg时血管再通率高,剂量再增加出血风险加大;②r-Sak在有效剂量范围内不激活犬的系统纤溶,但对犬的凝血系统影响较大。

参考文献/References:

[1]Vanderschueren S,Barrios L,Kerdsinchai P,et al.A rando-mized trial of recombinant staphylokinase versus alteplmase for coronary artery patency in acute myocardial infarction[J].Circulation,1995,92:2044-2050.
[2]LU JX,Shang XH,Fu JH,et al.Effects of recombinant staphylokinase on coronary thrombosis in Chineseexperimental miniature swine[J].Acta Pharmacol Sin,2002,23:509-515.
[3]刘圣,施海彬,季立标,等.介入技术建立犬急性脑栓塞动物模型的研究[J].南京医科大学学报,2005,25:76-79.
[4]施海彬,刘圣,黄峻,等.介入犬急性脑栓塞模型的建立及CT灌注成像早期诊断的研究[J].介入放射学杂志,2005,14:146-150.
[5]施海彬,徐大哲,胡卫星,等.动脉内尿激酶介入治疗急性脑梗死的评价[J].中华急症医学杂志,2002,11:301-306.
[6]Shi HB,Suh DC,Lim SM,et al.Outcome evaluation of intra-arterial infusion of urokinase for acute ischemic stroke[J].J Kor Radiolo Societ,2000,42:897-904.
[7]Higashida RT,Furlan AJ,Roberts H,et al.Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke[J].Stroke,2003,34:109-137.
[8]Pettersen JA,Hudon ME,Hill MD.Intra-arterial thrombolysis in acute ischemic stroke:a review of pharmacologic approaches[J].Expert Rev Cardiovasc Ther,2004,2:285-299.
[9]Donnan GA,Howells DW,Markus R,et al.Can the time window for administration of thrombolytics in stroke be increased[J]芽CNS Drugs,2003,17:995-1011.
[10]Lian Q,Szarka SJ,Ng KK,et al.Engineering of a staphylo-kinase-based fibrinolytic agent with antithrombotic activity and targeting capability toward thrombin-rich fibrin and plasma clots[J].J Biol Chem,2003,278:26677-26678.
[11]Collen D,Schlott B,Engelborghs Y,et al.On the mechanism of activator of human plasminogen by recombinant staphylokinase[J].J Biol Chem,1993,268:8284-8289.
[12]Armstrong PW,Burton J,Pakola S,et al.CAPTORS II investi-gators.Collaborative angiography patency trial of recombinant staphylokinase(CAPTORS II)[J].Am Heart J,2003,146:484-488.
[13]Moreadith RW,Collen D.Clinical development of PEGylated recombinant staphylokinase(PEG-Sak)for bolus thrombolytic treatment of patients with acute myocardial infarction[J].Adv Drug Deliv Rev,2003,55:1337-1345.
[14]Bokarewa M,Tarkowski A.Human alpha-defensins neutralize fibrinolytic activity exerted by staphylokinase[J].Thromb Haemost,2004,91:991-999.
[15]Combined intravenous and intra-arterial recanalization for acute ischemic stroke:the Interventional Management of Stroke Study[J].Stroke,2004,35:904-911.
[16]秦智勇,陈衔城,马端,等.重组葡激酶治疗实验性幼猪急性脑栓塞的量效研究[J].中国临床神经科学,2002,10:50-52.
[17]Lu Q,Li Y,Wen L,et al.Safety evaluation of recom-binant staphylokinase in rhesus monkeys[J].Toxicol Pathol,2003,31:14-21.
[18]Vanderschueren S,Dens J,Kerdsinchai P,et al.Randomized coronary patency trial of double-bolus recombinant staphylokinase versus frontloaded alteplase in acute myocardial infarction[J].Am Heart J,1997,134:213-219.
[19]Collen D,Van Hoef B,Schlott B,et al.Mechanism of activator of mammalian plasma fibrinolytic systems with streptokinase and with recombinant staphylokinase[J].Eur J Biochem,1993,216:307-314.
[20]Warmerdam PA,Vanderlick K,Vandervoort P,et al.Staphylo-kinase-specific cell-mediated immunity in humans[J].J Immunol,2002,168:155-161.
[21]Wu SC,Castellino FJ,Wong SL.A fast-acting,modular-struc-tured staphylokinase fusion with Kringle-1from human plasminogen as the fibrin-targeting domain offers improved clot lysis efficacy[J].J Biol Chem,2003,278:18199-18206.

相似文献/References:

[1]史跃,高从敬,孟宪俊,等.颅内动脉溶栓联合机械碎栓治疗急性脑梗死[J].介入放射学杂志,2008,(05):309.
 SHI Yue,MENG Xianjun,CAI Tingjiang,et al.Intracranial arterial thrombolysis and mechanical fragmentation in patients with acute infarction[J].journal interventional radiology,2008,(03):309.
[2]王悍 王精兵 张贵祥 王麟川.肝细胞癌动脉化疗栓塞术后并发脑梗死一例[J].介入放射学杂志,2005,(04):442.
 WANG Han WANG Jing-bing ZHANG Gui-xiang WANG Lin-chuan.Cerebral infarction aften transaterial shemoembolization for hepatocellular carcinoma a cage report[J].journal interventional radiology,2005,(03):442.
[3]陈军,黄清海,刘建民,等.缺血性脑血管病304例血管造影分析[J].介入放射学杂志,2009,(04):248.
 CHEN Jun,HUANG Qinghai,LIU Jianmin,et al.Digital subtraction angiography in patients with ischemic cerebrovascular diseases:an analysis of 304cases[J].journal interventional radiology,2009,(03):248.
[4]王成虎,施海彬,刘圣,等.重组葡激酶动静脉途径溶栓治疗犬急性脑梗死对照研究[J].介入放射学杂志,2007,(06):397.
 WANG Chen-hu,SHI Hai-bin,LIU Sheng,et al.A comparative study on administration routes of recombinant staphylokinase in canine model with acute cerebral infarction[J].journal interventional radiology,2007,(03):397.
[5]张冰,郑少俊,方淳,等.rt-PA动脉溶栓治疗急性脑梗死的疗效观察[J].介入放射学杂志,2007,(09):580.
 ZHANG Bing,ZHENG Shao-jun,FANG Chun,et al.Inter-arterial thrombolysis using rt-PA for acute cerebral ischemic stroke[J].journal interventional radiology,2007,(03):580.
[6]王灵枝,高红.经皮肺穿刺并发急性脑梗死一例[J].介入放射学杂志,2007,(11):792.
 WANG Ling-zhi,GAO Hong.A case of percutaneous lung puncture complicating with acute cerebral infarction[J].journal interventional radiology,2007,(03):792.
[7]田 洪,宋 川,范汝雄,等.动脉溶栓后脑再灌注损伤的临床救治探讨[J].介入放射学杂志,2011,(08):603.
 TIAN Hong,SONG Chuan,FAN Ru-xiong,et al.Discussion on the treatment of cerebral ischemia-reperfusion injuries following intra-arterial thrombolysis[J].journal interventional radiology,2011,(03):603.

备注/Memo

备注/Memo:
收稿日期:2006-06-06
基金项目:江苏省“135”医学重点人才项目(项目编号:135-55)
更新日期/Last Update: 2007-03-15