一种能评价溶拴和抗栓药的大鼠大脑中动脉血栓模型

局部用氯化铁损伤血管以造成动物大脑中动脉血栓，于血栓形成后２４ｈ观察大鼠脑梗塞范围、行为及脑病理改变。结果表明，本模型造成的脑梗塞及行为障碍特点与Ｔａｍｕｒａ等（１９８ｌ）［１］建立的大鼠局部脑缺血模型相一致。所造成的血栓为混合血栓。本研究还观察了阿司匹林对脑血栓的预防作用及尿激酶的治疗作用。阿司匹林及尿激酶均可降低脑梗塞范围，改善行为障碍。结果表明该模型既可以评价溶栓因子又可以检验抗栓因子，为研究抗血栓药物提供了一种较好的途径。     

乙酰丹酚酸A对大鼠大脑中动脉血栓所致局部脑缺血性损伤的保护作用

乙酰丹酚酸A(ASAA)是丹参有效成分的衍生物。用三氯化铁局部涂抹损伤血管形成大鼠大脑中动脉血栓模型。以脑梗塞范围、行为障碍、脑组织病理改变为观察指标,研究ASAA对大脑中动脉血栓所致局部脑缺血的预防作用。结果表明,ASAA50及100 mg·kg^-1iv可显著降低大鼠脑梗塞范围,改善行为障碍。脑组织检查中,ASAA100 mg·kg^-1组动物大脑中动脉内血栓形成极少或未形成,脑组织缺血病变较轻。以上结果提示,ASAA可能通过抑制脑血栓形成,从而减轻血栓形成所致的局部脑缺血性损伤。     

银杏叶提取物(EGb)对大鼠局部脑缺血及颈动脉血栓形成的保护作用

应用大鼠大脑中动脉梗塞和血栓形成导致缺血性脑卒中的实验模型,观察银杏叶提取物(EGb)对脑缺血面积和由缺血造成的行为障碍的影响。结果表明预防或治疗性iv大剂量EGb(200mg·kg^-1)均能显著减少脑缺血面积,明显改善大鼠脑缺血造成的行为障碍,其预防作用似优于治疗作用。预防性iv小剂量EGb(100mg·kg^-1)也能明显减少血栓形成性脑缺血面积,改善梗塞和血栓形成性脑缺血所致的行为障碍,与阳性对照药尿激酶和尼莫地平作用相同。实验还发现EGb有抑制大鼠电刺激颈总动脉的血栓形成的作用,且其对抗血栓形成强度具剂量依赖性。提示EGb对缺血性脑卒中和血栓形成有预防和治疗作用。     

异亚丙基莽草酸抗血栓作用的实验研究

目的研究异亚丙基莽草酸(ISA)对大鼠动静脉环路血栓、大脑中动脉栓塞及血小板聚集的对抗作用及机制。方法用动静脉环路血栓及三氯化铁致大脑中动脉栓塞(MCAT)模型观察药物作用;并研究了ISA体内、外给药对血小板聚集的影响。结果ISA 25,50,100及200 mg·kg^-1 ig均可显著降低大鼠体外血栓重量;ISA 50,100,200 mg·kg^-1 ig可明显改善MCAT模型大鼠神经症状;ISA 100及200 mg·kg^-1 ig MCAT模型大鼠脑梗塞范围分别下降27.8%和31.6%;另外,ISA体内、外给药对ADP和胶原诱导的血小板聚集有明显的抑制作用。结论ISA可能通过抗血小板聚集作用抑制血栓的形成。     

阿司匹林对大鼠局灶性脑缺血的保护作用及其机制

目的　探讨阿司匹林对大鼠局灶性脑缺血的保护作用及其机制。方法　利用大鼠大脑中动脉梗塞的模型,观察阿司匹林对缺血大鼠的行为障碍,脑梗塞面积,细胞凋亡峰,细胞内钙及血浆Ｃ反应蛋白的影响。结果　阿司匹林能明显改善行为障碍,显著降低缺血大鼠的脑梗塞面积,降低细胞凋亡峰,细胞内钙水平和血浆Ｃ反应蛋白。结论　阿司匹林对大鼠局灶性脑缺血具有保护作用,而且其作用机制与抗凋亡,降低细胞内钙及血浆Ｃ反应蛋白有关     

莽草对大鼠大脑中动脉血栓所致局部脑缺血性损伤的拮抗作用

目的：研究莽草酸（ＳＡ）对大脑中动脉血栓所致局部脑缺血的影响。方法：用三氯化铁局部涂抹损伤血管形成的大鼠大脑中动脉血栓模型（ＭＣＡＴ）观察ＳＡ对行为障碍程度、脑梗塞范围、脑水肿和缺血区脑血流的影响。结果：ＳＡ２５、５０ｍｇ．ｋｇ＾－１ｉｐ于ＭＣＡＴ前连续红药３ｄ可分涉及了梗塞范围５１％、４２％,使脑含水量由８０．７％降致７９．８％、７９．９％,并可改善行为障碍程度和缺血区脑血流量的降低,病理检查显     

葛根素对脑缺血/再灌注损伤的保护作用

目的研究葛根素对脑缺血/再灌注损伤的保护作用。方法本实验采用大鼠右侧大脑中动脉阻塞(MCAO)2 h,再灌注24 h模型,每组最终保证8只成活大鼠。MCAO前,药物组大鼠分别腹腔注射葛根素25,50,100 mg.kg^-1,尼莫地平0.7 mg.kg^-1,1次.d^-1,连续7 d。操作后,分别用Longa’s法、红四氮唑(TTC)染色法及干燥失重法来评价大鼠的神经功能状态、脑梗塞面积及脑水肿。结果与模型组比较,葛根素50,100 mg.kg^-1可明显减少大鼠MCAO后脑梗塞面积、降低脑水肿的程度及改善神经功能症状,具有显着性差异(P<0.05或P<0.01)。结论葛根素对大鼠脑缺血/再灌注损伤具有保护作用。     

尿激酶、低分子肝素治疗早期脑梗塞及预防复发

目的研究小剂量尿激酶对早期脑梗塞治疗效果及应用低分子肝素预防血栓复发的临床意义.方法 66例急性脑梗塞病人随机分为3组,分别给予大剂量尿激酶、小剂量尿激酶及低分子肝素、丹参注射液及阿司匹林治疗并观察疗效.结果小剂量尿激酶及低分子肝素组、大剂量尿激酶组疗效明显高于丹参组,有显著性差异（P＜0.05）,小剂量尿激酶组溶栓后血栓复发低于大剂量尿激酶组,疗效存在显著性差异（P＜0.05）,而且小剂量尿激酶组溶栓后出血明显少于大剂量尿激酶组,差异无显著性（P＞0.05）.结论早期脑梗塞应用小剂量尿激酶溶栓与大剂量尿激酶溶栓疗效相同,低分子肝素可有效防止血栓复发.     

血栓靶向尿激酶脂质体的制备及其体内溶栓效果

目的制备血栓靶向的尿激酶脂质体,并在大鼠颈总动脉血栓模型上考察其溶栓情况。方法通过液相合成法合成出靶向于血栓的特异性配体H-Arg-Gly-Asp-Ser-OH (RGDS),并将其与monocarboxyl poly (ethylene glycol) 3 500 distearoyl phosphatidylethalnolamine (DSPE-PEG_{3 500}-COOH)偶联后插入到脂质体双层膜中得到血栓靶向尿激酶脂质体;通过制备方法的改进,以氢化豆磷脂在室温下制备尿激酶脂质体;在大鼠颈总动脉血栓模型上,考察了血栓靶向脂质体的体内溶栓效果。 结果所得的尿激酶脂质体包封率高、粒径小,稳定性好;与空白对照组的栓重相比,在相同剂量(60 kU·kg^-1,小剂量)下,游离尿激酶组几乎无任何改变,尿激酶脂质体组血栓重量稍有减轻但无显著性差异,血栓靶向尿激酶脂质体组血栓重量明显减轻(P<0.001);干重时的情况略有不同。与同剂量的普通脂质体相比,血栓靶向尿激酶脂质体溶栓效果显著改善(湿重时P<0.01,干重时P<0.05),表现出明显的靶向溶栓能力。 结论所制备的血栓靶向尿激酶脂质体具有靶向溶栓的效果。     

醒脑抗栓灵对脑中风治疗作用的研究

观察醒脑抗栓灵对实验动物的镇静，抗血栓，减少脑梗塞面积作用。结果表明，静滴醒脑抗栓灵2.0g生药/kg，使小鼠自主活动数减少，同剂量对给予阈下剂量戊巴比妥钠的小鼠有明显的协同作用；2.0g生药／kg的醒脑抗栓灵和牛黄清心丸均使小鼠凝血时间明显延长，并能抑制大鼠体外,体内血栓的形成，尤对体内血栓抑制更为明显；静滴1.0g生药／kg醒脑抗栓灵，能减轻局部脑缺血大鼠的行为障碍和一定程度的减少脑梗塞面积的作用。     

Effects of intra-arterial urokinase on a non-human primate thromboembolic stroke model

One of the most important prognostic factors in the thrombolytic treatment of acute ischemic stroke is to re-canalize. The purpose of this study was to evaluate the effectiveness and safety of urokinase in a primate thromboembolic stroke model. Thromboembolic stroke was accomplished via occlusion of the middle cerebral artery (MCA) obtained by injecting an autologous blood clot into the left internal carotid artery in 21 male cynomolgus monkeys. Animals were randomly assigned to the following treatment groups: Group 1: vehicle (saline), Group 2: urokinase (40,000 IU), Group 3: urokinase (120,000 IU,) over 2 or 6 h via intra-internal carotid catheter starting 1 h after embolization, respectively. In the urokinase-treated groups, neurologic deficits were improved in consciousness and skeletal muscle coordination, but not sensory and motor systems. The infarction size in Group 2 (11.9 +/- 3.9% of the hemisphere) and 3 (7.6 +/- 2.5%) were significantly smaller than that (24.7 +/- 3.5%) in Group 1. However, 2 of 5 animals in Group 3 died. In conclusion, urokinase improved neurologic deficits and reduced cerebral infarction on thromboembolic stroke in the cynomolgus monkey.     

YM90K, an AMPA receptor antagonist, protects against ischemic damage caused by permanent and transient middle cerebral artery occlusion in rats

The neuroprotective effect of YM90K, a potent AMPA receptor antagonist, was examined in rats with permanent and transient occlusion of middle cerebral artery (MCA) using intraluminal suture occlusion method. In rats with permanent MCA occlusions, two types of occluders were used to compare the efficacy of YM90K. When a 4–0 (diameter: 0.19 mm) suture was used, YM90K (20 mg kg^–1 h^–1 i.v. infusion for 4 h) significantly reduced infarct volume (P<0.05) and neurologic deficits (P<0.05) 24 h after MCA occlusion. Infarct volume was also reduced by YM90K at the same dose (P<0.01) when severe ischemia was induced by a 3–0 (diameter: 0.23 mm) suture. In rats with transient (3 h) MCA occlusions, a 10-mg kg^–1 h^–1 dose of YM90K that did not show significant protection in rats with permanent MCA occlusion offered neuroprotective effects. These data demonstrate that YM90K provides cerebral neuroprotection against a wide range of ischemic insults. Received: 19 June 1998 / Accepted: 2 September 1998     

急性脑梗死r-tPA静脉溶栓治疗临床疗效观察

目的探讨重组组织型纤溶酶原激活物(r-tPA)静脉溶栓治疗急性脑梗死的临床疗效。方法溶栓组(28例)急性脑梗死患者进行r-tPA静脉溶栓治疗,36例急性脑梗死患者未溶栓分为对照组,采用常规阿司匹林片等治疗。比较两组患者治疗前、治疗后1 h、24 h、14 d及30 d的美国国立卫生研究院卒中量表(NIHSS)评分,以及治疗前、治疗后30、60、90 d评定Barthel指数(BI)。结果溶栓组疗效明显优于对照组,溶栓组出现脑出血转化2例,死亡1例。对照组脑出血转化1例,死亡1例。两组无明显全身性出血。结论 r-tPA静脉溶栓治疗能明显促进急性脑梗死患者神经功能缺损早期恢复,能够改善预后,提高患者的生活质量。     

Role of endogenous tPA in stroke]

The role of endogenous tissue-type plasminogen activator (tPA) on focal cerebral ischemic injury (FII) after middle cerebral artery (MCA) occlusion was studied by using tPA gene deficient (KO) mice and wild type (WT) mice. MCA was occluded by thrombosis induced by 3 different intensities of photochemical damage of MCA. FII size in KO mice was smaller than in WT mice in mild damage whereas it was larger in severe damage. These results suggested that endogenous tPA protected FII through its thrombolytic action on transient occlusion with mild damage, but deteriorated on persistent occlusion with severe damage. Cerebral hemorrhage associated with antithrombotic and thrombolytic therapy in acute stroke is a major clinical problem. We investigated the roles of endogenous tPA and MMPs in hemorrhagic cerebral infarction associated with heparin. We demonstrated that heparin administration caused cerebral hemorrhage in WT but not in KO. Heparin administration increased tPA activity and its mRNA expression in WT. We also observed an induction of MMP9 and its mRNA expression by heparin administration in WT but not in KO. Our findings suggest that endogenous tPA plays an important role in heparin-produced cerebral hemorrhage via MMP9 induction and activation.     

尿激酶静脉溶栓治疗急性脑梗死临床分析

目的 观察静脉注射尿激酶溶栓治疗急性脑梗死的临床疗效及安全性。方法 采用静脉注射国产尿激酶（天普洛欣）200万U／人次,治疗急性脑梗死28例,以同期住院的30例常规治疗病人作为对照。结果 溶栓组28例中24h内基本痊愈4例,显效8例,而对照组无1例有效。治疗后14d溶栓组基本痊愈12例,显效6例,对照组基本痊愈1例,显效3例。溶栓组不同时间的显效率均经对照组高,有显性差异（P＜0．05）。 结论 静脉注射尿激酶治疗超早期脑梗死疗效明显。     

丁基苯酞对局部脑缺血大鼠行为和病理改变的保护作用

观察了丁基苯酞对大鼠右侧大脑中动脉阻断(MCAO)后行为和脑梗塞面积的影响。结果表明,MCAO后15min丁基苯酞po或ip,均能降低局灶型脑缺血大鼠的脑梗塞面积和改善各种神经症状,疗效与MK801(0.5mg·kg^-1,ip)相当,优于尼莫地平(1.0mg·kg^-1.sc)。提示丁基苯酞可能是一个有开发前途的抗脑缺血药物。     

尿激酶溶栓治疗急性心肌梗死疗效观察

目的判断尿激酶静脉溶栓治疗急性心肌梗死(AMI)的疗效。方法回顾分析我科1997年2月-2005年2月应用尿激酶(150万u,30 min内静滴)治疗69例AMI患者的临床症状、心电图、心肌酶谱的变化及不良反应,根据冠脉再通间接指征判断冠脉再通率。结果冠脉再通率达到73.9%,69例患者溶栓后早期(24h内)T波倒置49例,其中冠脉再通43例,早期T波未倒置20例中冠脉再通8例。结论AMI患者早期使用尿激酶静脉溶栓安全可靠,疗效满意,溶栓后早期T波倒置对判定冠脉再通有重要价值。     

Antithrombotic effect of a novel tissue plasminogen activator from the venom of Gloydius brevicaudus viper

OBJECTIVE To investigate the thrombolytic and antiplatelet effects of a novel plasminogen activator from the venom of Gloydius brevicaudus viper(GBV-PA)in vitro and in vivo.METHODS Thrombolytic experiments were performed in rabbit models of ear vein thrombosis and carotid artery thrombosis,and in dog model of acute cerebral infarction.Inhibition of thrombus formation was evaluated in rat inferior vena cava thrombosis model and ferric chloride-induced arterial thrombosis.In vitro,we assayed the antithrombotic effect of GBV-PA on rabbit blood clots,euglobulin lysis time(ELT)of rabbit plasma,and on ADP-induced platelet aggregation.RESULTS GBV-PA intravenous administ ration significantly reduced vascular recanalization times of rabbit ear veins thrombosis and thrombus weight of rabbit carotid artery thrombosis.The arterial recanalization rates were dose-and time-dependently improved after administration of GBV-PA in canine acute cerebral infarction model.Thrombus length and weight was significantly reduced by GBV-PA both in rat inferior vena cava and ferric chloride-induced arterial thrombosis models.Thrombus formation of blood of rabbits they were administrated with GBV-PA was also inhibited.GBV-PA radically reduced plasma ELT of rabbit′s blood clots.ADP-induced platelet aggregation was inhibited by GBV-PA in a dose-dependent manner with a half-maximal inhibitory concentration of 19.9μg·mL-1.CONCLUSION This study demonstrates that GBV-PA is a thrombolytic and antiplatelet agent.It has significant antithrombotic effects on various in vitro and in vivo experimental models of thrombosis.The mechanisms that underline its antithrombotic effects were related to GBV-PA′s capabilities of increasing fibrinolytic activities and inhibition of platelet aggregation.     

尿激酶静脉溶栓治疗急性进展性脑梗死对血液流变学的影响和疗效判断

目的观察尿激酶(UK)静脉溶栓治疗急性进展性脑梗死的疗效及对血液流变学的影响。方法对发病在6～24h以内的急性进展性脑梗死72例患者随机分为3组,其中发病6～12h以内20例为治疗A组,发病12～24h内22例为治疗B组,和对照组(C组30例),两治疗组均应用尿激酶100万～200万U静脉滴注之后应用常规治疗,对照组应用常规治疗。结果治疗组采用的尿激酶静脉溶栓总有效率、神经功能缺损恢复的程度上、血液流变性的改善均明显优于对照组(P<0.05),但两治疗组间无显著差异(P>0.05)。结论尿激酶静脉溶栓治疗发病6～24h以内的无溶栓禁忌证的急性进展性脑梗死是安全、有效的,能显著改变血液流变性。