脑梗死患者溶栓治疗前后血脂和凝血功能参数变化

目的探讨脑梗死患者溶栓治疗前后血脂水平和凝血功能参数的变化,为临床治疗脑梗死提供科学依据。方法 (1)对81脑梗死患者根据头部CT或MRI病灶大小,梗死体积按Pullicino公式(长×宽×层数/2)计算进行分组:大梗死组(病灶体积>10cm~3)10例,中梗死组(病灶体积4~10cm~3)22例,小梗死组(病灶体积<4cm~3)49例,设健康对照组50例。(2)分别在溶栓治疗前24小时内、溶栓治疗后24h内、第3天和第7天采集脑梗死组血标本,进行血脂指标:甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白AI(APOAI)、载脂蛋白B(APOB)和脂蛋白(a)[Lp(a)];凝血功能指标:凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)和血浆D二聚体(D-D)检测及统计学分析。结果 (1)大、中、小梗死组溶栓治疗前24h内TG、TC、LDL-C、APOAI、APOB和Lp(a)高于对照组(P<0.01),HDL-C低于对照组(P<0.05);大梗死组溶栓治疗前24h内TG、TC、LDL-C、APOAI、APOB和Lp(a)高于小梗死组(P<0.05)。(2)大梗死组溶栓治疗前24h内TG、TC、HDL-C、LDL-C、APOAI、APOB和Lp(a)与溶栓治疗后24h内、第3天和第7天比较差异无统计学意义(P>0.05)。(3)大、中、小梗死组溶栓治疗前24h内FIB和D-D高于对照组(P<0.01),PT和APTT低于对照组(P<0.05),TT无统计学差异(P>0.05)。(4)大梗死组溶栓治疗前24h内FIB和D-D高于小梗死组(P<0.05),PT、APTT和TT较小梗死组无统计学差异(P>0.05)。(5)大梗死组溶栓治疗后24h内、第3天和第7天D-D、PT和APTT明显高于溶栓治疗前24h内水平(P<0.01)。结论脑梗死患者溶栓治疗前后血脂水平和凝血功能指标有明显变化,其水平变化可作为脑梗死治疗及预后的判断指标。     

磷酸肌酸钠对脑梗死的保护作用

目的观察磷酸肌酸钠对脑梗死的影响,探讨其对脑梗死的保护作用。方法 Wistar大鼠60只随机分成3组:假手术组、脑梗死组、磷酸肌酸钠组(PCr组),每组20只。观察大鼠的神经功能缺损评分。脑缺血6 h后将大鼠处死,检测血清及脑匀浆SOD、MDA、GPX活性,计算脑梗死体积,观察大鼠海马组织的超微结构。结果脑梗死组大鼠神经功能缺损评分与PCr组比较,差异有统计学意义(P<0.05)。脑梗死组和PCr组大鼠血清及脑组织匀浆内SOD、GPX、MDA水平与假手术组比较,差异有统计学意义;脑梗死组和PCr组之间比较,差异也具有统计学意义(P<0.05)。PCr组大鼠的梗死体积较脑梗死组明显减小(P<0.05)。结论 PCr可减少脑缺血后神经功能缺损评分,缓解缺血后脂质过氧化程度,降低脑梗死体积,减轻神经细胞损伤。     

探讨rPA静脉溶栓治疗急性脑梗死的临床价值

目的：探讨rPA静脉溶栓治疗急性脑梗死的临床价值。方法选取2010年4月~2015年4月我院收治的38例符合中国脑血管防治指南中规定的溶栓条件的急性脑梗死患者,均行rPA静脉溶栓治疗,观察并记录所有患者治疗前及治疗后的神经功能缺损评分（ NIHSS）,评价其临床疗效。结果本组38例患者治疗后NIHSS平均得分为（12.52±1.63）分,31例患者治疗24h后的 NIHSS评分变化大于4分,治疗有效率为81.58%。结论 rPA静脉溶栓治疗急性脑梗死疗效显著,能有效改善患者神经功能缺损症状,安全可靠,但治疗期间须注意患者凝血功能,若发现APTT异常需立即采取相应处理措施。     

CA-074Me对大鼠脑缺血再灌注损伤保护作用的研究

目的探讨CA-074Me对大鼠脑缺血再灌注损伤保护作用。方法将90只SD大鼠随机分为假手术组(n=10),脑缺血再灌注模型组(n=40),CA-074Me治疗组(n=40)。线栓法制备大脑中动脉梗死(MCAO)模型,TTC染色检测脑梗死体积,TUNEL法原位检测神经细胞凋亡。结果模型组大鼠脑缺血再灌注后1 h后TTC染色即可显示梗死灶,同时神经细胞凋亡计数明显增多(P<0.05),CA-074Me 治疗可明显减少大鼠脑缺血再灌注后脑梗死体积(P<0.05),及其神经细胞凋亡计数(P<0.05)。结论 CA-074Me 治疗能减轻大鼠脑缺血再灌注损伤。     

当归内酯治疗大鼠局灶性脑缺血的作用机制

目的观察当归内酯对局灶性脑缺血大鼠的治疗,并探讨其作用机制。方法线栓法堵塞大脑中动脉起始处,造成大鼠局灶性脑缺血(MCAO),缺血2 h后行神经功能评分。随机将模型大鼠分为当归内酯高、低剂量组和模型组,于再灌04、h时分别灌服受试药物80、20 mg.kg-1或等体积溶媒;假手术组同时灌服等体积溶媒。再灌24 h,各组大鼠再行神经功能评分,经TTC染色法测定脑组织梗死面积,免疫组化方法检测诱导型一氧化氮合酶(iNOS)在脑组织中的表达,分光光度法测定脑组织中iNOS活性及NO含量。结果当归内酯能够显著减小MCAO所致大鼠的脑梗死面积(P<0.01),明显改善MCAO大鼠的神经症状(P<0.01),降低缺血脑组织中iNOS的表达量、酶活性以及NO水平(P<0.05或P<0.01)。结论当归内酯对大鼠局部脑缺血损伤具有明显的保护作用,其机制可能与降低缺血脑组织中iNOS表达量及其酶活性、抑制NO的细胞毒有关。     

促红细胞生成素和血管紧张素受体拮抗剂对脑缺血再灌注后梗死体积和脑组织水肿的影响

目的研究促红细胞生成素(EPO)和血管紧张素受体拮抗剂(ARB)对脑缺血后的脑保护作用。方法采用健康的SD大鼠,线栓法阻断一侧大脑中动脉血流2 h,再灌注24 h,建立局灶性脑缺血再灌注损伤模型(MCAO),治疗组分别予缺血再灌注前后经腹腔注射EPO 3 000 IU/(kg·d),或缬沙坦40 mg/(kg·d),评价大鼠神经功能,测定其脑梗死体积占全脑体积的百分比、脑组织的含水量。结果与缺血再灌注组相比,EPD处理组可改善神经功能缺失,减少脑梗死体积,降低梗死组织含水量,且经EPD预处理,改善更明显,差异有统计学意义(P<0.05);与缺血再灌注组相比,ARB处理组可减少脑梗死体积,降低梗死组织含水量,差异有统计学意义(P<0.05)。结论 EPD和ARB可减少脑梗死体积,降低梗死组织含水量,EPD可明显改善神经功能缺失,经EPD和ARB预处理改善更为明显,具有良好的脑保护作用。     

血管内成栓脑梗死模型的制备及评价

目的建立大鼠血管内成栓脑梗死模型并对其病理特征进行评价。方法使用直流电刺激颈总动脉制造血栓,通过血流引导碎栓堵塞中动脉,制造脑栓塞模型。通过测定脑血流、脑梗死体积、动物行为学等指标,评价模型特点,并观察了组织型纤维蛋白酶原激活剂(tissue plasminogen activator,t-PA)的溶栓作用。结果脑梗死大鼠的病灶区血流量降低至基准值的30%左右,并在造模24h后表现出明显的神经功能与运动功能失调,脑组织出现明显的梗死灶。使用t-PA进行溶栓治疗后可以明显改善上述病理特征。结论大鼠血管内成栓脑梗死模型适用于进行血栓性脑梗死病理研究与药物溶栓作用评价。     

急性脑梗死尿激酶静脉溶栓疗效观察

目的观察尿激酶静脉溶栓治疗急性脑梗死的临床有效性及安全性。方法应用大剂量尿激酶超早期(发病6h内)静脉溶栓治疗急性脑梗死23例,于溶栓前及溶栓后2h、24h、1个月进行神经功能缺损评分,同时观察脑内及其他系统有无出血并发症。结果溶栓后2h瘫痪肢体肌力提高3级4例,2级8例,1级7例,无变化4例,其中4例24h内临床症状反复;1个月时,发病4h内溶栓组与4h~6h内溶栓组相比,神经功能缺损评分值(ESS)升高更明显,前者(P<0.01),后者(P<0.05),本组有1例大面积脑梗死溶栓后出现非症状性出血性脑便死,3例于溶栓结束后出现轻微齿龈出血,无1例死亡。结论大剂量尿激酶静脉溶栓治疗急性脑梗死其疗效较肯定,溶栓开始时间越早,疗效越好,在严格掌握适应症情况下,应用比较安全。     

依达拉奉对脑梗死大鼠神经保护作用最佳治疗时间窗的探讨

目的：采用大鼠大脑中动脉梗塞( MCAO)模型,探讨依达拉奉治疗急性脑梗死的最佳治疗时间窗。方法将MCAO模型大鼠随机分为A、B、C、D和E组(n=10)。 A、B、C、D组分别于造模后0.5 h、1 h、1.5 h、2 h通过尾静脉给予3 mg/kg的依达拉奉,E组于造模后给予等量的生理盐水。于梗死后24 h进行神经功能缺损评分,并测量脑梗死体积。结果 A、B、C组神经功能缺损评分和脑梗死体积均低于E组(P<0．05,P<0．01),其中B组与E组比较差异更显著(P<0．01),B组低于A、C、D组(P<0．05,P<0．01),B组与D组比较差异更显著(P<0．01)。结论对大鼠MCAO模型,依达拉奉具有神经保护作用,且其神经保护作用有治疗时间窗。     

降纤酶对血栓形成和光化学诱导大鼠脑缺血的影响

目的:探讨降纤酶对血栓形成和光化学诱导大鼠脑缺血的影响。方法:①对血栓形成的影响:10只大鼠分为生理氯化钠溶液对照组及降纤酶治疗组(每组各5只),采用微循环方法观察降纤酶治疗后肠系膜血栓溶解情况,分别在光照后1,2,5,10min记录对照组及治疗组血栓体积及占管腔体积比。②对光化学诱导大鼠脑缺血的影响:72只大鼠以光化学法制成左顶叶皮层缺血模型,治疗组于缺血后1,3,6,9,12,24h由尾静脉注射降纤酶8U·kg~(-1)),对照组按相同时间点用等量生理氯化钠溶液尾静脉注射。进行神经功能评分,缺血48h后处死,标本用HE及TTC染色,观察梗死灶病理改变及测定梗死灶体积。结果:①对血栓形成的影响:降纤酶治疗组血栓体积明显减小,占管腔体积百分比减少,与对照组相比有显著性差异(P<0.05)。②对光化学诱导大鼠脑缺血影响:缺血1,3,6h治疗组神经功能评分改善,脑梗死体积明显减小,与对照组相比有极显著性差异(P<0.01),相应时间点病理改变轻于对照组。缺血9h给药组神经功能评分有改善,脑梗死体积亦较对照组小,统计学有显著差异(P<0.05)。12和24h治疗组与对照组相比无显著差异(P>0.05)。结论:降纤酶能有效溶解肠系膜血栓并减小光化学诱导大鼠脑梗死体积。     

Neuroimaging, biochemical and cellular evidence of protection by mycophenolate mofetil on middle cerebral artery occlusion induced injury in rats

Stroke is a major cause of mortality and disability worldwide. Presently, recombinant tissue plasminogen activator is the only approved drug for the management of acute ischemic stroke. However, it has limitations like narrow therapeutic window and increased risk of intracranial hemorrhage. In previous studies, immunosuppressive agents such as cyclosporine A and tacrolimus have shown neuroprotection by improving neurological functions and infarct volume in models of ischemic stroke. Therefore, the present study was designed to evaluate the effect of mycophenolate mofetil (MMF) on the cerebral ischemic injury in the middle cerebral artery occlusion (MCAo) model in rats. MCAo was carried out in male Wistar rats by inserting an intraluminal thread. One hour after MCAo, the animals were treated with MMF (50, 100, 200mg/kg, i.p.). Reperfusion was done after 2h of occlusion. Thirty minutes after reperfusion, animals were subjected to diffusion-weighted magnetic resonance imaging for assessment of neuroprotective effect of MMF. Twenty four hours after MCAo, motor performance was assessed and the animals were euthanized for estimation of brain malondialdehyde, glutathione, myeloperoxidase and nitric oxide levels. The effect of MMF on apoptosis was also evaluated. MMF significantly attenuated the percent infarct area, apparent diffusion coefficient and signal intensity as compared to a vehicle treated group. Treatment with MMF prevented the motor impairment and significantly reversed the changes in levels of malondialdehyde, glutathione, myeloperoxidase and nitric oxide. MMF treatment significantly reduced the apoptosis. Data of the present study indicate neuroprotective effect of MMF in the experimental model of ischemic stroke.     

高压氧对急性缺血性脑卒中的疗效研究

目的研究高压氧（HBO）辅助溶栓治疗急性缺血性脑卒中的疗效。方法选择2010年6月～2011年6月来本院治疗的46例急性缺血性脑卒中患者为研究对象,根据治疗方法不同分为高压氧治疗组（HBO组）16例和对照组30例。高压氧治疗组在脑卒中发作后接受药物治疗,3～5d开始接受高压氧治疗,对照组只接受药物治疗,未接受高压氧治疗。比较两组患者早期（发病后2周）和晚期（发病1个月后）的临床疗效。结果两组患者的NIHSS评分在治疗初期和第一次评估时差异无统计学意义（P=0.140）,但两组NIHSS评分在治疗1个月时,差异有统计学意义（P〈0.01）。结论高压氧治疗急性缺血性脑卒中是有效的,尤其在远期预后方面,效果更佳。     

Pretreatment with eplerenone reduces stroke volume in mouse middle cerebral artery occlusion model

Eplerenone, a mineralocorticoid receptor antagonist, is reported to be effective to prevent end-stage cardiovascular damage induced by aldosterone. However, the effect of eplerenone on brain damage is not fully understood. Here, we investigated whether pretreatment with eplerenone attenuates stroke size in mice subjected to middle cerebral artery occlusion. Middle cerebral artery occlusion with a microfilament technique induced focal ischemia, to approximately 25% of the total area in a coronal section of the brain. Treatment with eplerenone at a dose of 1.67 mg/g chow significantly reduced the ischemic area, ischemic volume, and neurological deficit, without a blood pressure-lowering effect. Laser-Doppler flowmetry analysis showed a decrease in surface cerebral blood flow in the peripheral region after 1 h of middle cerebral artery occlusion. This decrease was smaller in mice treated with eplerenone. Superoxide production evaluated by staining with dihydroethidium was attenuated in the ischemic area of the brain in eplerenone-treated mice. Taken together, our findings suggest that eplerenone has a protective effect on ischemic brain damage, at least partly due to improvement of cerebral blood flow in the penumbra and reduction of oxidative stress.     

Enhanced neuroprotection and reduced hemorrhagic incidence in focal cerebral ischemia of rat by low dose combination therapy of urokinase and topiramate

Thrombolysis is increasingly being used in treating acute ischemic stroke but it is also accompanied with a serious complication of cerebral hemorrhage in a dose-dependent fashion. As a lower dose may result in decreased effectiveness, we tested the efficacy of combining a neuroprotective agent, topiramate (TPM), with lower doses of intra-arterial urokinase in an embolic stroke model. Focal ischemia was produced by introduction of an autogenous thrombus into the right middle cerebral artery. Urokinase was infused via the ipsilateral internal carotid artery and neuroprotective agent, TPM, was administrated intra-peritoneally 2 h following ischemic insult. The animals were assigned to five groups: (1) control group (n=6); (2) urokinase 5000 units/kg (n=8); (3) urokinase at 2500 units/kg (n=8); (4) topiramate at 20 mg/kg (n=8); (5) urokinase at 2500 units/kg and topiramate at 20 mg/kg (n=8). Neurobehavioral outcome and the degree of brain infarct volume were assessed at 24 h. Three animals in the group treated by high dose urokinase developed intracranial hemorrhage but none in other groups. Animals in all medication-groups showed significant improvement in neurobehavioral score. Post-ischemia treatment with urokinase or TPM alone significantly attenuated brain infarct volume (low-dose urokinase, 39.1+/-13.0%, p<0.05; high-dose, 18.4+/-8.5%, p<0.001; TPM, 20. 1+/-11.2%, p<0.001) when compared to the control (54.2+/-9.04%). Addition of TPM to low dose urokinase achieved better neuroprotection (8.2+/-6.0%) than any single-drug-treated groups. Our data suggests that combination of low dose urokinase with a neuroprotective agent may benefit ischemic stroke treatment by improving neurologic recovery, attenuating infarction size, and reducing the risk of cerebral hemorrhage.     

基层医院急诊室内使用瑞替普酶与小分子肝素治疗急性ST段抬高型心肌梗死的疗效评价

目的：比较瑞替普酶（rPA）与小分子肝素（依诺肝素）对急性ST段抬高型心肌梗死（STEMI）患者急诊静脉溶栓治疗的临床疗效。方法观察2008年11月~2010年10月间在本院急诊室内接受rPA或尿激酶溶栓并辅助普通肝素或依诺肝素抗凝治疗的72例STEMI患者,在血管再通率、心脏功能恢复程度、出血不良反应及预后等方面的差异。结果 C组（rPA＋肝素）和D组（rPA＋依诺肝素）溶栓再通率均明显高于A组（尿激酶＋肝素）、B组（尿激酶＋依诺肝素）,且平均再通时间也明显缩短（P〈0.05）。心脏彩超提示,治疗3个月后C、D组心脏功能的恢复更为明显。此外,B、D组轻度出血的发生率比A、C组降低（P〈0.05）。结论 rPA辅助依诺肝素适合基层急诊室内进行STEMI的静脉溶栓治疗。     

急性缺血性脑梗死的动脉溶栓治疗

目的 :探讨急性脑梗死行局部动脉内溶栓治疗的临床疗效及安全性。方法 :2 8例自起病至溶栓时间在 1h～ 12h之内的急性脑梗死患者 ,经股动脉插管行全脑血管造影术发现闭塞血管后 ,先用导丝及微导丝通过血栓到达血栓远端 ,撤出导丝后将导管置于靶血管闭塞点或患侧颈内动脉内 ,用注射泵缓慢注射尿激酶行局部溶栓治疗。结果 :2 8例中 14例完全再通 ,8例部分再通 ,6例无效 ,2 4h ,1个月 ,3个月NIHSS评分 ,分别较溶栓前≤ 4分 ,治疗后 3个月神经功能恢复有效率为 70 % (2 2 / 2 8) ,3例合并无症状性脑出血均痊愈。结论 :本组患者血管再通率为 70 % ,经股动脉插管行急性缺血性脑梗死动脉溶栓治疗可使闭塞血管再通 ,此疗法是目前治疗脑梗死有效的治疗手段     

Hemorrhagic transformation in focal cerebral ischemia: influence of time to artery reopening and tissue plasminogen activator

We used an adaptation of a well-established rat model of middle cerebral artery occlusion (MCAO) that is both minimally invasive and reproducible to determine the effects of time to reperfusion and administration of tissue plasminogen activator (t-PA) on the development of hemorrhagic transformation (HT) in a rat model of acute stroke. Animals were randomized to receive either t-PA 10 mg/kg (29 rats) or an equal volume of saline (29 rats) over 20 minutes, beginning 5 minutes before reperfusion. Time to artery reopening varied between 1 and 24 hours after MCAO in both groups. At 18-24 hours after ischemia, the animals were sacrificed and their brains were preserved for analysis of HT. Logistic regression was used to determine the influence of time on HT risk and calculate the time at which 50% of animals developed HT (HT50%). At 24 hours, HT was present in 17 of 29 animals in each group and was significantly influenced by the time of artery reopening: 3 (15%) of 20 animals reperfused less than 3 hours after onset of ischemia and 32 (84%) of 38 reperfused 3 or more hours after the onset of ischemia (p<0.001). There was no difference in HT50% between groups. Time to artery reopening is an important determinant of HT risk in this model of cerebral ischemia. This model may have utility in developing strategies to reduce HT formation after thrombolytic therapy in patients with acute stroke.     

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.     

糖酐酯对高血糖大鼠溶栓治疗的影响

目的：探讨高血糖与溶栓治疗后白细胞浸润的关系，以及糖酐酯对高血糖大鼠溶栓治疗的影响。方法：通过复制高血糖大鼠模型，自体血栓栓塞大脑中动脉，缺血30分钟静脉予以糖酐酯或生理盐水，缺血2小时经颈外动脉注入尿激酶溶栓，观察缺血24小时浸润白细胞数及梗死灶大小，结果：缺血24小时，高血糖大鼠溶栓组与正常血糖大鼠溶栓组比较，缺吉边区浸润白细胞数明显增多（P＜0．01），梗死灶增大（P＜0．05），高血糖大鼠联合糖酐酯溶栓组较高血糖大鼠溶栓组浸润白细胞数减少（P＜0．01），梗死灶减少（P＜0．05），与正常血糖大鼠溶栓组比较，白细胞数减少（P＜0．05），梗死灶虽有减少的趋势，但差异无显著意义。结论：高血糖通过增加白细胞浸润加重溶栓治疗后且织损伤；糖酐酯可以抑制高血糖大鼠溶栓治疗后白细胞的浸润，减小梗死灶。     

一站式CT扫描指导颈内动脉夹层致急性缺血性卒中的保守治疗

目的 探讨一站式CT扫描对颈内动脉夹层(ICAD)致急性缺血性卒中内科保守治疗的指导意义.方法 选择解放军第180医院2014年3月至2017年3月行一站式CT扫描检查确诊的ICAD致急性缺血性卒中患者临床资料,其中侧支循环好、脑组织灌注好的患者16例(研究组),侧支循环差、脑组织灌注差且拒绝介入手术开通的患者21例(对照组),均进行静脉溶栓或抗凝治疗,评估入出院NIHSS评分改善情况、3个月后改良Rankin评分量表(mRS)评分、半年时血管再通情况及并发症发生率、死亡率等.结果 2组入出院时NIHSS评分变化,研究组明显优于对照组(P<0.05).2组3个月后临床预后对比,研究组明显优于对照组(P<0.05).研究组血管再通率明显高于对照组(P<0.05).2组患者症状性颅内出血、高灌注脑病等并发症的发生率比较差异无统计学意义(P>0.05).研究组患者病死率明显低于对照组(P<0.05).结论 通过一站式CT扫描评估ICAD致缺血性卒中患者的侧支循环及脑组织灌注情况,于对于侧支循环开放、脑组织灌注好的患者及早行溶栓或抗凝治疗,提高闭塞血管再通率,有助于改善临床预后,降低并发症发生及死亡率,提高患者生存质量.