国产r-SAK对兔股动脉血栓的溶栓效果

目的观察不同剂量国产r-SAK对兔股动脉血栓的溶栓效果,并探讨其满意的治疗剂量。方法新西兰兔20只,随机分为对照组(NS 10 mL)、r-SAK小剂量组(r-SAK0．25 mg·kg-1)、中剂量组(r-SAK 0．5 mg·kg-1)、大剂量组(r-SAK 1．0 mg·kg-1),用球囊损伤法建立兔右股动脉血栓形成模型,球囊损伤后120 min经耳缘静脉输注治疗药物,时间均为30 min,实验过程中持续监测兔股动脉压力变化。对部分动物溶栓前后行股动脉造影。结果①球囊损伤后2 h,各实验组右侧股动脉脉压均下降为0或小于左侧脉压的10％;②溶栓后部分兔右股动脉脉压增加至大于左侧脉压的50％,其中对照组0只,小剂量组2只,中剂量组5只,大剂量组5只;③中、大剂量组血管再通率显著高于对照组,且较小剂量组有升高趋势。各剂量组再通时间及开通持续的时间无显著差异。中、大剂量组溶栓后右侧股动脉的血流状况有优于小剂量组的趋势;④溶栓后5 h,所有再通血管脉压均下降至左侧脉压的50％以下;⑤股动脉造影及病理检查均显示溶栓后部分血管再通。结论国产r-SAK对兔股动脉血栓有显著溶栓作用,剂量>0．5 mg·kg-1时溶栓再通率达100％。     

国产重组葡激酶对兔血小板及凝血、纤溶系统的影响

目的　观察国产重组葡激酶 (r SAK)对兔血小板及凝血、纤溶系统的影响。方法　新西兰兔 4 0只 ,随机分为以下 8组 :①对照组 (生理盐水 10ml,30min) ,②r SAK小剂量组 (1 5× 10 4U/kg ,30min) ,③r SAK中剂量组 (3 0× 10 4U/kg ,30min) ,④r SAK大剂量组 (6 0× 10 4U/kg ,30min) ,⑤r SAK单次静脉推注组 (3 0× 10 4U/kg ,2min) ,⑥联合肝素治疗组 (先静脉推注肝素 2 0 0U/kg ,继之予r SAK3 0× 10 4U/kg ,30min ,输注完毕予肝素 5 0U·kg 1·h 1静脉滴注至观察终点 ) ,⑦尿激酶 (UK)组 (3 0× 10 4U/kg ,30min) ,⑧重组链激酶 (r SK)组 (3 0× 10 4U/kg ,30min)。用球囊损伤法建立兔右股动脉血栓形成模型 ,继而用输液泵经兔耳缘静脉匀速注入上述溶栓药物。在给药前、给药后 30min、6 0min、12 0min取静脉血检测血小板计数、凝血酶原时间 (PT)、部分凝血活酶活化时间 (APTT)、凝血酶时间 (TT)、纤维蛋白原 (Fg)、纤溶酶原 (Plg)、α2 抗纤溶酶 (α2 AP)和D二聚体 (D dimer)。结果　各治疗组在给药前、后血小板计数较对照组均无显著差异。r SAK各剂量组、UK组和r SK组给药后血浆Fg均有显著下降。中、小剂量r SAK给药后 12 0minPT延长 (P <0 0 5 ) ;UK及r SAK单独治疗组给药后APTT和TT均无显著延长     

重组链激酶与尿激酶治疗急性心肌梗死的对比研究

目的观察重组链激酶（r-SK）与尿激酶（UK）静脉溶栓治疗急性心肌梗死的疗效。方法将93患者随机分成r-SK组48例和UK组45例,均给常规治疗,r-SK组,r-SK150万单位＋5%葡萄糖100mL;UK组,UK150万单位＋5%葡萄糖100mL,观察冠状动脉再通率、不良反应及5周病死率。结果r-SK组总再通率81.25%,6h内再通率为86.49%,与UK组比较,差异均有统计学意义（P〈0.05）;2组在出血、心律失常、过敏、低血压及5周后死亡率上,差异无统计学意义（P〉0.05）。结论r-SK较UK的心肌梗死血管再通率高,药效较好,也具有不良反应和并发症少的特点,是值得临床上推广应用。     

生物法测定重组葡激酶在股动脉血栓形成模型兔中的药动学参数

目的:研究重组葡激酶(r-SAK)在股动脉球囊损伤后血栓形成模型兔中的药动学。方法:采用自制大块玻璃平板和琼脂井式扩散生物法测定分别静脉不同方式给予r-SAK不同剂量后的兔的血药浓度。结果:r-SAK的药动学特征符合二室模型,血浆检测浓度在20~2500IU/ml范围内与溶圈直径线性关系良好(r=0·9960),平均回收率为(96·05±9·20)%。低、中、高3个剂量静脉滴注组峰浓度分别为(2·28±1·06)、(3·54±0·32)、(6·12±1·61)μg/ml,单次静脉推注组峰浓度为(5·16±1·02)μg/ml。结论:生物法检测r-SAK血药浓度简便、可靠。     

重组链激酶与尿激酶治疗急性心肌梗死的对比研究

目的 观察重组链激酶（r-SK）与尿激酶(UK)静脉溶栓治疗急性心肌梗死的疗效。方法 将93患者随机分成r-SK组48例和UK组45例,均给常规治疗,r-SK组,r-SK150万单位+5％葡萄糖100 mL;UK组,UK150万单位+5％葡萄糖100 mL,观察冠状动脉再通率、不良反应及5周病死率。结果 r-SK组总再通率81.25%,6 h内再通率为86.49%,与UK组比较,差异均有统计学意义（P<0.05）;2组在出血、心律失常、过敏、低血压及5周后死亡率上,差异无统计学意义（P>0.05）。结论 r-SK较UK的心肌梗死血管再通率高,药效较好,也具有不良反应和并发症少的特点,是值得临床上推广应用。     

国产重组链激酶与尿激酶治疗急性心肌梗死疗效对比观察

目的 :评价国产重组链激酶 ( r- SK)与尿激酶 ( U K)治疗急性心肌梗死 ( AMI)的疗效 ,并比较二者差异。方法 :74例符合溶栓条件的 AMI患者分为 UK治疗组 39例和 r- SK治疗组 35例 ,均采用静脉注射溶栓治疗 ,观察冠状动脉再通率、出血、35 d病死率、低血压并发症以及 r- SK的不良反应。结果 :溶栓治疗后临床梗死相关血管再通率r- SK组为 77.14 % ,显著高于 UK组 5 6 .4 1% ( P<0 .0 5 ) ,两组的出血、35 d病死率、低血压等并发症无显著性差异( P>0 .0 5 )。结论 :本研究提示国产 r- SK治疗 AMI临床再通率高于 U K,不良反应相似 ,无严重出血 ,是安全、有效的溶栓药物     

尿激酶溶栓治疗早期急性脑梗死的疗效

目的评价在急性脑梗死(ACI)病后6h尿激酶(UK)静脉溶栓的临床疗效。方法78例ACI随机分成UK组和对照组。UK组UK25万U静脉注射,续以UK150万U60min内静脉滴注,对照组采用通常的治疗方案,评价治疗前和治疗后1、7、14、28d的神经功能缺损评分。结果①治疗后1、7、14、28d时UK组与对照组比较改善均非常显著(P<0.01);7d时UK组改善比较显著(P<0.05);②UK组用药前与用药后1d比较、7d与14d比较、14d与28d比较,神经功能缺损评分改善均非常显著(P<0.01),用药1d与7d比较,差异显著(P<0.05);③UK组用药后1d时显效率23.3%,7d时56.1%,14d时80.3%,28d时91.6%,均高于同期对照组结果(P<0.01、<0.01、<0.01、<0.05)。结论早期ACIUK溶栓治疗比常规治疗起效快、作用强、效果好,并且安全、简便、可靠。     

重组TGF_α-PE40对动脉球囊损伤后内膜增生的抑制作用(英文)

目的:探讨基因重组转化生长因子α-绿脓杆菌外毒素融合蛋白(TGF_α-PE40;TP40)对动脉球囊损伤后内膜增生的抑制作用。方法:40只雄性兔随机分为TP4015μg、30μg、60μg、正常动脉及生理盐水对照组(n=8),均高脂饲养。在兔右颈总动脉行球囊内膜剥脱术后24h,治疗组于动脉损伤段局部给予TP40 15μg、30μg及60μg治疗;对照组给予生理盐水。正常动脉组局部给予TP40 60μg。于治疗后第2周取实验动脉段行光镜、电镜观察及计算机图像分析。结果:光镜观察见对照组动脉内膜不规则增厚,新生内膜可见大量平滑肌细胞(SMC),管腔狭窄;TP40治疗组动脉内膜增生被明显抑制,管腔无狭窄;TP40对正常动脉影响不大;电镜观察见TP40 60μg治疗组的动脉中膜有较多变性、坏死的SMC;计算机图像分析显示动脉损伤后第2周TP40治疗组内膜截面积及内膜与中膜截面积的比值显著小于生理盐水对照组(P<0.01)。结论:TP40对动脉球囊损伤后的内膜增生具有抑制作用。     

MMP-9在大鼠局灶性脑缺血UK溶栓引起的再灌注损伤及出血性转化中的作用

目的:探讨基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)在大鼠局灶性脑缺血应用尿激酶(urokinase,UK)溶栓引起的再灌注损伤及出血性转化中的作用。方法:将实验动物随机分成UK溶栓组和线栓法缺血再灌注组。分别用免疫组织化学方法分析2组缺血后24h MMP-9的表达。结果:缺血后24h2组均有MMP-9的表达,但是UK溶栓组表达的程度明显高于线栓法缺血再灌注组。结论:UK溶栓法相较于机械法再灌注在MMP-9表达方面有明显的不同,UK溶栓组MMP-9表达明显上调。     

右美托咪定对胰肾联合移植术胰腺缺血-再灌注损伤的保护作用

目的 探讨右美托咪定对胰肾联合移植术胰腺缺血-再灌注损伤的保护作用.方法 60例行胰肾联合移植术患者均分为右美托咪定(D)组和对照(C)组.麻醉诱导后,D组静脉输注右美托咪定0.5 μg/kg(12min内),继之0.5 μg·kg1·h-1静脉泵注至手术结束.C组相同时点静脉输注等容量生理盐水.麻醉诱导后(T0)、切...     

Thrombolytic efficacy of native recombinant staphylokinase on femoral artery thrombus of rabbits

AIM: To investigate the thrombolytic efficacy, ideal dosage and administration of native recombinant staphylokinase (r-SAK). METHODS: Forty New Zealand rabbits were randomly assigned into the control, r-SAK low-dose, medial-dose, high dose, single bolus, allied therapy, recombinant streptokinase (r-SK) and urokinase (UK) groups. The right femoral artery thrombosis models were made by balloon injury, and 120 min after the injury, the thrombolytic agents were infused through the rabbits' parallel-ear vein. RESULTS: (1) 2 h after balloon injury, the pulse pressures of the right femoral arteries reduced to 0 or less than 10% of that of left femoral arteries in all groups; (2) after thrombolytic therapy, the pulse pressures in some of the femoral arteries markedly enhanced to more than 50% of that of left femoral arteries; (3) the reopening rates in the r-SAK medial and high dose groups were significantly higher than that of the control. The reopening rate of the same dose native r-SAK was significant higher than that of UK and r-SK; (4) the patency score of the right femoral arteries tended to be better in the r-SAK medial and high-dose groups than that of the low-dose group, and the time to reopening in the allied therapy group tended to be shorter. CONCLUSION: (1) r-SAK has a definite thrombolytic effect on the femoral artery thrombus of rabbits; (2) single bolus is an effective manner of r-SAK therapy, and r-SAK allied therapy with heparin may shorten the time to recanalization; (3) the efficacy of the same dose native r-SAK was superior to that of r-SK and UK.     

The usefulness of systemic administration of recombinant human tissue-type plasminogen activator in femoral arterial thrombolysis of rabbits

The thrombolytic effect of locally or systemically administered recombinant human tissue-type plasminogen activator (rt-PA) was investigated in comparison with the effect of tissue culture urokinase (TCUK), using a model of femoral artery thrombosis in rabbits. An 125I-labeled fibrinogen thrombus was formed in the femoral artery following injury of the intima by diluted sulfuric acid, and thrombolytic activity was evaluated one hour after the end of infusion of the agents. Local infusion of rt-PA (500-10,000 IU/kg) and TCUK (10,000 IU/kg) induced a marked thrombolysis. When rt-PA and TCUK were injected systemically in a high dose (200,000 IU/kg), rt-PA but not TCUK had a significant thrombolytic activity. In these cases, rt-PA was not accompanied by systemic activation of the fibrinolytic system, as evaluated by unaltered levels of alpha 2-antiplasmin in the plasma, while TCUK led to a substantial decrease in the alpha 2-antiplasmin level. These results suggest that systemically administered rt-PA but not TCUK induce a significant thrombolysis without systemic activation of the fibrinolytic system in cases of peripheral artery thrombosis.     

不同溶栓方法治疗AMI对再通和PLT的影响

目的研究不同静脉溶栓方法在AMI（急性心肌梗死）溶栓再通及PLT（血小板）变化。方法将95例AMI随机分为两组,观察组48例,UK（尿激酶）30万U静推,120万U静滴溶栓治疗AMI;对照组47例,UK静滴溶栓治疗AMI,研究两组治疗后再通率和PLT变化。结果观察组溶栓再通率和PLT聚集率明显优于对照组,观察组溶栓再通率为64．58％,对照组为51．06％,差异有显著性（P〈0．05）。结论观察组比对照组溶栓再通率高且PLT聚集显著。     

不同年龄组急性心肌梗塞溶栓治疗的对比研究

４７例急性心肌梗塞（ＡＭＩ）患者按发病年龄随机分成三组，进行尿激酶（ＵＫ）溶栓疗效的对比研究。结果表明，１２小时内溶栓的４７例ＡＭＩ患者再通率、死亡率和并发症发生率分别为５５．３％、１４．９％和８．５％。６小时内溶栓再通率老年组（５０％）明显低于青年组（８０％）和老年前期组（７０％）。老年组住院病死率为２５．９％，且有出血并发症发生，而青年组和老年前期组无一例死亡且无一例出血并发症发生。提示ＵＫ溶栓疗效与患者年龄有关，老年人溶栓疗效较差，病死率和出血并发症发生率较高。     

尿激酶溶栓治疗急性心肌梗死

目的探讨尿激酶对急性心肌梗死(AMI)患者溶栓后血管再通率的影响。方法将83例AMI患者随机分为溶栓组(A组)和非溶栓组(B组),溶栓时间窗选择在12 h以内。所有AMI患者均给予常规治疗。A组:立即给予尿激酶1 500 000 U加0.9%氯化钠溶液100 mL静滴,30 min内滴完。溶栓开始后每隔12 h皮下注射低分子肝素钙0.4 mL,连用5 d。B组:给予硝酸甘油、低分子肝素钙及其他常规治疗。观察两组冠状动脉血管的再通情况、再灌注性心律失常及轻微出血发生率。结果两组冠状动脉血管再通率比较,差异有统计学意义(69.77%vs 27.50%,χ2=14.811 0,P<0.01);再灌注性心律失常、轻微出血发生率比较,差异无统计学意义(16.28%vs 12.50%,11.63%vs 10.00%,均P>0.05)。结论尿激酶静脉溶栓治疗能够显著提高AMI患者的冠状动脉再通率,是一种治疗AMI安全、简便、有效的抢救措施,将对AMI患者的预后产生积极的影响。     

替罗非班联合尿激酶超选择动脉溶栓治疗急性大脑中动脉栓塞的实验研究

目的:探讨替罗非班联合尿激酶超选择性溶栓治疗急性大脑中动脉栓塞的疗效和安全性。方法:采用兔自体血栓栓塞大脑中动脉制成急性脑梗死模型,随机分为替罗非班组(T组)、尿激酶组(UK组)、替罗非班+尿激酶组(T+UK组)和对照组。采用X线数字减影(DSA)观察动脉内超选择溶栓的血管再通率,磁共振弥散成像观察相对表观弥散系数(rADC),改良Bederson评分法观察神经功能缺损。24h后处死动物,经氯化-2,3,5-三苯基四氯唑染色,进行光镜病理形态学检查。结果:T+UK组血管再通率为80%,病理检查未见明显出血,rADC值、神经功能缺损评分、脑梗死面积均优于T组、UK组和对照组。结论:早期使用替罗非班联合尿激酶进行动脉内溶栓在兔超早期脑缺血模型中疗效优于单纯尿激酶动脉内溶栓。     

Pharmacokinetic and thrombolytic properties of unglycosylated recombinant tissue-type plasminogen activator (BM 06.021) produced in Escherichia coli

Summary Recombinant tissue-type plasmogen activator (rt-PA) was produced in Escherichia coli cells in order to obtain an unglycosylated rt-PA (BM 06.021) with increased thrombolytic potency due to altered pharmacokinetic properties. The pharmacokinetics were studied in rabbits upon intravenous infusion of 200 kU/kg over 30 min. The thrombolytic dose-response effects were evaluated in a rabbit model with ¹²⁵I-labeled venous thrombi upon intravenous infusion over 4 h. The thrombolytic effects after intravenous bolus injection of 200 kU/kg BM 06.021 were investigated in a canine model of coronary artery thrombosis. All studies were performed comparing BM 06.021 with glycosylated rt-PA (alteplase).BM 06.021 demonstrated a longer (p < 0.05) half-life (5.6±2.6 vs. 2.1±0.3 min) and a lower (p(0.05) clearance rate (7.5±0.8 vs. 22.2±3.1 ml ·min^–1·kg^–1) than alteplase in rabbits upon intravenous infusion. The doseresponse curve of BM 06.021 for thrombolysis in a rabbit model of jugular vein thrombosis was located to the left of that for alteplase with a 2.1-fold lower effective dose of 50% thrombolysis (ED₅₀) of BM 06.021 (207 vs. 436 kU/kg). Intravenous bolus injection of 200 kU/kg BM 06.021 induced the same reperfusion rate (4/6) as intravenous infusion of 800 kU/kg alteplase over 90 min in a canine model of coronary artery thrombosis. The residual thrombus wet weight did not significantly differ between BM 06.021 and alteplase (5.7 ± 1.8 vs. 6.3 ± 1.1 mg).The results indicate that unglycosylated rt-PA (BM 06.021) has a higher in vivo thrombolytic potency than glycosylated rt-PA (alteplase). The increased potency seems to be due to the altered pharmacokinetic properties of BM 06.021, because the in vitro specific fibrinolytic activities of BM 06.021 and alteplase are virtually identical (783 vs. 800 kU/mg). Send offprint requests to U. Martin at the above address     

肝素加尿激酶对急性心肌梗死的疗效观察

目的：评价肝素的使用时机对急性心肌梗死再灌注的影响。方法：收治住院符合ST段抬高的急性心肌梗死溶栓标准的患者66例,将其分为观察组33例和对照组33例。均给予尿激酶1500000U加入100ml0.9%氯化钠溶液中,于30min内静脉输注溶栓。观察组于溶栓前即刻给予普通肝素5000U静推。结果：观察组尿激酶溶栓后再通率为87.88%,对照组溶栓后再通率为66.67%,两者比较,差异有统计学意义（P〈0.05）。结论：尿激酶溶栓前即刻静脉输注肝素能显著提高冠状动脉血管再通率,改善患者预后,不会增加临床出血的危险。     

重组组织型纤溶酶原激活物早期静脉溶栓治疗急性脑梗死的临床研究

目的探讨重组组织型纤溶酶原激活剂早期静溶栓治疗急性脑梗死的疗效及安全性。方法回顾性分析笔者所在医院80例急性脑梗死患者的临床资料,发病时间<6h的患者给予rt-PA50mg静脉溶栓治疗,溶栓前及溶栓后30min、24h、14d及3个月分别采用美国国立卫生院卒中量表(NIHSS)评分,溶栓后3个月给予修订的Rankin评分和日常生活能力Barthal指数评分,评价其疗效及安全性。结果溶栓后各时间点NIHSS评分均有明显改善,组间比较无显著性差异(均P>0.05);≤6h治疗其1h、3h、24h再通率效果显著,明显优于另两组(均P<0.05);≤6h治疗再出血的发生情况明显低于另两组(均P<0.05)。结论 ACI发病6h内给予rt-PA静脉溶栓治疗相对安全有效。