尿激酶静脉溶栓治疗急性心肌梗死疗效观察

目的观察尿激酶静脉溶栓治疗急性心肌梗死的疗效。方法17例符合溶栓适应证的急性心肌梗死患者,在常规治疗的同时,给予尿激酶100万U静滴,溶栓治疗后观察胸痛的程度以及心律、心率和血压的变化;心电图严密监测,在3h内每隔30min记录1次12导联心电图,并根据病情随时记录,以后1次/d,观察ST段抬高和下降的变化以及各类心律失常。结果有11例符合再通指标,再通率为64.7%,病死者2例,均为冠脉未通患者。结论尿激酶静脉溶栓疗效可靠,方法简便,易于掌握。     

rt-PA应用后MMP-2、MMP-9表达的改变及Neuroserpin的影响

目的 观察重组组织型纤溶酶原激活剂(rt-PA)对血管再通后基质金属蛋白酶-2(MMP-2)、MMP-9表达的影响以及神经源性丝氨酸蛋白酶抑制剂(neuroserpin,NSP)的干预作用。方法 应用易卒中型肾血管性高血压大鼠复制大脑中动脉缺血模型,缺血3 h后再灌注并静脉注射rt-PA,于预组在应用rt-PA前脑内注射NSP,1天后处死,常规病理检查,并应用免疫组织化学和原位杂交的方法观察MMP-2、MMP-9在脑组织的表达。结果 缺血再灌注后MMP-2、MMP-9表达均升高;应用rt-PA后可见缺血再灌注区有灶性出血及红细胞漏出,同时使MMP-9进一步升高,但对MMP-2影响不大;应用rt-PA的同时使用NSP可以减轻缺血损伤,减少出血的发生,并使升高的MMP-9减少至接近正常水平,但NSP可以使MMP-2表达略有升高。结论 rt-PA溶栓后出血转化的发生可能与MMP-9表达增加有关,溶栓时联合应用NSP可能通过降低rt-PA所致的MMP-9表达上调而减轻溶栓治疗的出血并发症。     

重组组织型纤溶酶原激活剂早期静脉溶栓对急性脑梗死的疗效

目的 评价重组组织型纤溶酶原激活剂（rt-PA） 6 h内静脉溶栓治疗急性脑梗死的疗效及剂量.方法 将符合入选标准的206例患者随机分为A、B、C组,A组rt-PA 0.9 mg/kg,B组rt-PA 0.7 mg/kg,C组为对照组,不用rt-PA;每组又各分为两个亚组,低分子肝素组（A1、B1、C1）和非低分子肝素组（A2、B2、C2）.采用“中国脑卒中临床神经功能缺损评分标准”（CSS）及Barthel指数（BI）评定溶前及溶后24 h、3 d、7 d、90 d的疗效.结果 90 d各组的有效率：A组79.80%,B组86.55%,C组63.70%;90 d显效率：A组68.75%,B组74.85%,C组42.05%;90 d痊愈率：A组46.05%,B组39.45%,C组21.10%;90 d病死率：A组11.76%,B组10.39%,C组18.03%;以上各项A＋B组与C组差异有统计学意义,A与B组差异无统计学意义,而低分子肝素组与非低分子肝素组差异无统计学意义.各组总出血发生率： A组20.59%,B组18.18%,C组0;各组48 h内脑出血率：A组8.82%,B组6.49%,C组0;14 d脑出血率：A组10.29%,B组7.79%,C组0;各项A＋B组与C组差异有统计学意义,A与B组差异无统计学意义.症状性脑出血率：A组1.47%,B组2.60%,C组0,A＋B组与C组差异无统计学意义,低分子肝素组与非低分子肝素组差异无统计学意义.90 d重度致残率＋病死率：A组23.52%、B组22.08%、C组32.79%,A＋B组与C组差异有统计学意义.结论 rt-PA 6 h内静脉溶栓治疗急性脑梗死90 d有效率、显效率、痊愈率较对照组显著提高.rt-PA 6 h内静脉溶栓治疗急性脑梗死是安全有效的.溶栓剂量0.7 mg/kg与 0.9 mg/kg疗效基本相同,对于部分高龄体弱的中国人,0.7 mg/kg可能更为安全经济.     

卒中溶栓规范化管理：特殊临床状态的rt-PA溶栓治疗

在我国，由于缺乏循证医学证据，卒中急性期患者的溶栓治疗方案基本上是参考国外相关指南确定的，其是否适合国人尚无科学依据。另一方面，临床工作中存在的一些模糊或尚无定论的问题需要深入探讨、得出结论以造福患者。本文就这些问题作一简要综述以期达到抛砖引玉的效果。     

依达拉奉对脑缺血大鼠重组组织型纤溶酶原激活剂溶栓后金属蛋白酶9表达的影响

目的 观察依达拉奉对脑缺血大鼠重组组织型纤溶酶原激活剂（rt-PA）溶栓后基质金属蛋白酶9（MMP-9）的表达的影响,探讨依达拉奉对溶栓后脑组织的保护作用。方法 采用大鼠自体血栓栓塞大脑中动脉闭塞（MCAO）模型,112只入选的SD大鼠分为假手术组（A组）、模型对照组（B组）、rt-PA溶栓组（C组）及依达拉奉联合rt-PA组（D组）,每组大鼠28只。应用红四氮唑染色观察各组大鼠脑梗死的体积百分比,同时进行神经功能缺损程度评分（SSS）,免疫组织化学方法检测各组大鼠脑MMP-9的表达及相应病理学检查。结果 与模型对照组比较,rt-PA溶栓组比较,脑梗死体积百分比及SSS评分降低,MMP-9表达明显降低（P＜0.05～0.01）。与rt-PA溶栓组比较,依达拉奉联合rt-PA组脑梗死体积百分比及SSS评分降低,MMP-9表达明显降低（P＜0.05～0.01）。结论 依达拉奉可有效的抑制rt-PA溶栓后的大鼠脑梗死范围增大,抑制MMP-9的过度表达,从而减轻对血脑屏障的破坏,进而可能延长溶栓治疗的时间窗,进一步阻止脑梗死体积扩大和改善神经功能。     

MMP-9在扩大时间窗急性脑梗死静脉溶栓出血转化中的意义

目的探讨基质金属蛋白酶-9(MMP-9)与扩大时间窗至发病6 h内急性脑梗死重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗的关系。方法对70例本院神经内科扩大时间窗内行rt-PA静脉溶栓的急性脑梗死患者分别测定溶栓前后的血浆MMP-9水平,并与急性脑梗死非溶栓对照组比较。结果急性脑梗死患者溶栓组、非溶栓对照组入院12 h后血浆MMP-9水平和入院时比较都有显著差异(P<0.05);有出血转化者MMP-9水平皆较无出血转化为高(P0.05)。结论急性脑梗死MMP-9表达水平与出血转化...     

普罗布考对大鼠脑出血后MMP-9表达及血-脑屏障通透性的影响

目的讨论普罗布考对大鼠脑出血后基质金属蛋白酶-9(MMP-9)的表达及血-脑屏障通透性的影响。方法采用自体动脉血注入大鼠尾壳核建立脑出血模型,将7 5只大鼠分成对照组、脑出血组、普罗布考组。各实验组分12h、1d、3d、5d、7d五个时间点,每个时间点5只大鼠。分别采用逆转录聚合酶链法(RT-PCR)、蛋白印迹法(Western blot)、伊文思兰染色法测定不同时间点的MMP-9 mRNA、MMP-9蛋白的表达和血-脑屏障通透性的变化。结果 MMP-9 mRNA、MMP-9蛋白的表达和血-脑屏障通透性在脑出血后1d开始升高,3d达到高峰,5d⁷d开始下降。给予普罗布考治疗后,在1d、3d、5d、7d时间点MMP-9蛋白和血-脑屏障通透性明显下调,与脑出血组相比差异有统计学意义(P<0.01),而MMP-9 mRNA无明显变化(P>0.01)。12h时间点MMP-9蛋白和血-脑屏障通透性在普罗布考组与脑出血组差异无统计学意义(P>0.01)。结论普罗布考可以减轻大鼠脑出血后的MMP-9蛋白的高表达,降低血-脑屏障的通透性,从而减轻脑水肿程度。     

积极开展急性缺血性卒中的静脉溶栓治疗

<正>脑卒中为我国的多发病和常见病,病死率和病残率均显著高于欧美国家,已成为我国国民首位死亡原因,超过肿瘤和冠心病[1]。鉴于缺血性卒中发病率高于出血性卒中的特点,其早期诊断、早期治疗应成为当前各医疗中心临床工作及科研的重点。在目前开展的急性缺血性卒中的治疗方法中,以超早期溶栓、卒中单元、抗血小板药物和发病后早期开始的规范化康复治疗为十分有效的管理和治疗方法。而发病后超早期溶栓则是最具针对性     

rt-PA溶栓治疗急性缺血性脑卒中后脑出血的研究 进展

重组组织型纤溶酶原激活物（rt-PA）溶栓治疗急性缺血性脑卒中（AIS）后脑出血是溶栓治 疗中的严重并发症。rt-PA在局部溶栓的同时增加了机体出血风险，可能导致脑出血性转化（CHT），其发 病与纤溶酶原激活物抑制剂1（PAI1）和凝血酶激活的纤溶抑制物（TAFI）的基因多态性和生理差异有关。 体温、年龄、头颅CT或MRI的影像表现、血压和血糖等多种因素均是影响rt-PA 溶栓治疗AIS 后脑出血 的因素。在rt-PA 溶栓治疗中，针对不同生理状态和临床特征的AIS 患者进行预见性地监测和目的性地 护理具有重要的临床意义。     

机械性碎栓联合静脉窦接触性溶栓治疗颅内静脉窦血栓

目的探讨机械性碎栓联合静脉窦接触性溶栓治疗颅内静脉窦血栓形成的疗效和安全性。方法 12例颅内静脉窦血栓形成病人,先经微导管缓慢注入尿激酶10~20万U,再利用微导丝进行机械性碎栓,随后经微导管缓慢注入尿激酶药物溶栓,保留微导管于静脉窦内继续溶栓3~5 d。结果静脉窦部分再通11例,完全再通1例。出院时痊愈9例,遗留轻度神经功能障碍2例,死亡1例,无手术相关的并发症。随访11例,时间6~18个月,痊愈10例。结论采用机械性碎栓联合静脉窦接触性溶栓治疗能迅速恢复静脉窦顺向血流,是安全有效的介入治疗方法,但溶栓药物的选择、用量、介入治疗的长期疗效等问题仍有待进一步研究。     

Effects of ischemic preconditioning on blood-brain barrier permeability and MMP-9 expression of ischemic brain

The study was designed to investigate the effects of ischemic preconditioning (IP) on permeability of blood-brain barrier (BBB) and expression of matrix metalloproteinase-9 (MMP-9) in subsequent ischemic hemisphere. Rats were divided into four groups, one group was used as control, and the other three groups were given three different pretreatments: the first group received a saline injection into the right internal carotid artery (SI), the second group underwent both left and right carotid arteries occlusion (BCAO), and the third group was treated with BCAO and SI simultaneously (BS). After 24 hours of pretreatments, the focal cerebral ischemia was induced by inserting a thread into the right middle cerebral artery causing occlusion (MCAO). Brain water content, BBB permeability and MMP-9 expression of ischemic hemisphere brains were measured at 24 and 48 hours after MCAO. After 24 and 48 hours MCAO, averages for brain water content were 82.92 and 83.12% in BS group, 85.19 and 85.73% in SI group and 86.06 and 85.88% in BCAO group. Evans blue content of ischemic hemispheres were 14.01 and 11.74 microg/mm(3) at 24 and 48 hours after MCAO in BS group, which were lower than the other two groups, 16.22, 15.01 and 16.61, 15.58 microg/mm(3), respectively (p<0.01). The expression levels of MMP-9 in ischemic hemisphere in BS were lower than that in other two groups (p<0.01). Therefore, ischemic preconditioning could ameliorate brain edema and BBB disruption caused by subsequent cerebral ischemia. Ischemic preconditioning could decrease MMP-9 protein and mRNA expression, which may be an important mechanism of cerebral ischemic tolerance.     

Hemorheology in systemic ultrahigh-dose thrombolytic therapy with streptokinase and urokinase

The course of fibrinogen (Fgen), red cell aggregation (RCA), plasma viscocity (PV), platelet aggregation (PA) and hematocrit (Hc) was studied in patients with ultrahigh - dose thrombolytic therapy (1.5 x 10(6) units/hour for 6 hours = 1 cycle) with streptokinase (SK) or urokinase (UK) over a period of 3 cycles. Both ultrahigh - dose SK and UK produced significant changes in the course of Fgen, RCA and PV, whereas PA (spontaneous and ADP-induced) and Hc remained unchanged. After termination of each cycle Fgen progressively increased while RCA and PV further decreased. The extent of alteration in cycle 1 - concerning the baseline values - was more pronounced with SK than with UK, but the overall effect of SK decreased through the consecutive cycles because of more rapid increase during the SK-free period. In UK-therapy hemorheological alterations were initially moderate but increased from cycle to cycle.     

溶栓治疗急性脑梗死患者血浆基质金属蛋白酶-9含量变化及临床意义

目的 探讨急性脑梗死患者尿激酶动脉溶栓治疗后血浆基质金属蛋白酶-9(Matrix metalloproteinases-9,MMP-9)的变化及临床意义.方法 对20例尿激酶动脉溶栓治疗的急性脑梗死患者MMP-9基础值和溶栓后水平进行测定,比较溶栓前后以及与健康对照组血浆MMP-9水平.结果 急性脑梗死患者溶栓后MMP-9水平比对照组和基础值显著升高(P<0.05);溶栓后发生出血性转化的患者MMP-9水平较溶栓前有显著增加(P<0.05),与无出血患者相比有增高趋势但无统计学差异;溶栓后完全再通患者MMP-9较基础值明显升高(P<0.05).结论 尿激酶溶栓可能激活了MMP-9,增加溶栓后出血的风险,并且MMP-9可能参与了脑组织缺血再灌注损伤.     

Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injuryOBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3,6,12 hours, 1,2,4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter it gradually decreased.CONCLUSION: MMP-9 expression increases in rat brain tissue after focal cerebral ischemia/reperfusion injury, which correlates with increased permeability of the BBB.     

Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury**☆

BACKGROUND： The integrity of the blood brain barrier （BBB） plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 （MMP-9） is closely related to cerebral ischemia/reperfusion injury OBJECTIVE： This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability. DESIGN, TIME AND SETTING： This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006. MATERIALS： Ninety healthy male SD rats, aged 3-4 months, weighing 200-280 g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody （Boster, Wuhan, China） and Evans blue （Sigma, USA） were also used. METHODS： All rats were randomly divided into 9 groups with 10 rats in each group： normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3, 6, 12 hours, 1, 2, 4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled. MAIN OUTCOME MEASURES： BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method. RESULTS： All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter it grad     

促红细胞生成素对大鼠脑缺血再灌注后血脑屏障通透性和ZO-1表达的影响

目的研究促红细胞生成素(erythropoietin,EPO)预处理对大鼠脑缺血再灌注后血脑屏障通透性和紧密连接蛋白ZO-1的影响。方法采用大鼠大脑中动脉栓塞(MCAO)模型,伊文思蓝渗透性实验检测血脑屏障通透性,免疫组化法和Western blot法测定ZO-1蛋白表达,RT-PCR法测定ZO-1 mRNA表达。结果 EPO预处理能够明显减轻脑缺血再灌注后血脑屏障的通透性(P<0.01),并显著上调缺血脑组织中ZO-1蛋白及mRNA的表达水平(P<0.01)。结论 EPO通过上调脑缺血再灌注后脑组织中ZO-1的表达,降低BBB通透性,这可能是EPO保护脑缺血再灌注后神经组织的机制之一。     

脑出血灶周组织ICAM-1与MMP-9表达的实验研究

目的研究大鼠实验性脑出血后血肿周围脑组织细胞间粘附分子-1（ICAM-1），基质金属蛋白酶-9（MMP-9）的表达。方法采用立体定向技术将自体不凝血注入大鼠尾状核区制备脑出血模型，免疫组化染色法检测血肿周围脑组织ICAM-1，MMP-9的表达。结果脑出血后6h血肿旁有少量ICAM-1表达阳性细胞，12h开始增多，3d达高峰；脑出血后6h血肿周围就有较多MMP-9表达阳性细胞，2d时阳性细胞最多；脑出血后ICAM-1与MMP-9的表达呈正相关（y=0．768，P〈0．05）。结论血肿周围组织ICAM-1、MMP-9表达上调提示两者可能参与了脑出血后继发性脑损伤。     

体外溶栓试验确定急性脑梗死治疗中尿激酶用量的研究

目的 探讨体外溶栓试验确定尿激酶用量进行急性脑梗死溶栓治疗的效果。方法 对急性脑梗死患者立即应用体外溶栓试验,寻找处于溶柞状态的尿激酶用量进行溶栓,以后持续7d应用尿激酶40万U维持溶枪治疗,在溶栓治疗不同时间进行神经功能缺损程度评分及测定纤维蛋白原（Fbg）浓度、聚合反应速率（FMPV）、最大吸光度（ODmax）、FMPV／ODmax.结果 溶栓治疗组疗效明显高于非溶栓组（P〈0．05）,〈6h治疗纰疗效优于6～24h治疗组,6～24h治疗组优于非溶栓组（均P〈0．05）。Fbg浓度、FMPV、FMPV／ODmax溶栓后开始下降,而于溶栓后24h反弹达到高峰,随后再下降,于第5d再次显著升高,与溶栓后其他时间段相比差异显著性（均P〈0．05）,ODmax无明显变化。溶栓组并发出血1例（2．17％）,非溶栓组无出血患者。结论 应用体外溶栓试验确定尿激酶用量进行急性脑梗死溶栓治疗是安全有效的。