人工寒潮促发脑卒中的实验研究

目的　探索建立人工寒潮环境 ;探讨人工寒潮与脑卒中的关系。方法　观测用经改装的冷藏柜及人工气候箱模拟寒潮时所需条件及达标情况 ;分别将复制成功的易卒中型肾血管性高血压大鼠 (RHRSP)及正常大鼠置于人工寒潮环境中 ,观察大鼠的血压波动、脑血管病变及脑卒中的发生情况。结果　冷藏柜与人工气候箱均能模拟寒潮 ,后者除能控制温度外同时能控制相对湿度 ;人工寒潮来临时RHRSP组大鼠血压波动大、自发性脑卒中明显增多 ,与对照组比较有明显差异 (P <0 0 5 )。结论　人工气候箱较冷藏柜能更好模拟寒潮 ,人工模拟寒潮克服了季节限制且一致性好、易重复 ;人工寒潮可以使RHRSP发生脑卒中 ,可较好模拟气温骤降 (自然寒潮 )时的脑卒中 ,为进一步研究寒潮诱发脑卒中的机制提供了条件     

人工寒潮时不同血压水平大鼠脑卒中发病的实验研究

目的探讨人工寒潮时不同血压水平对脑卒中发病的影响。方法360只大鼠分为寒潮和非寒潮2大组,再按血压水平各分为正常血压组、160～199mmHg、200～219mmHg和≥220mmHg等4个亚组,观察大鼠的脑卒中情况。结果脑卒中发生率在血压<220mmHg与≥220mmHg的大鼠、寒潮组与非寒潮组之间均有显著性差异。脑动脉病变严重的卒中率更高。Logistic回归发现只有寒潮前高血压是脑卒中发生的唯一独立危险因素。结论高血压、寒潮与脑卒中发病密切相关,脑动脉病变是患病基础,高血压是脑卒中的独立危险因素,而寒潮是重要的启动因子。     

降纤酶治疗脑梗死的实验研究

目的观察降纤酶对光化学模型诱导的大鼠大脑中动脉血栓的溶栓作用及对脑梗死灶的影响.方法应用光化学方法造成60只易卒中型肾血管性高血压大鼠(RHRSP)大脑中动脉(MCA)血栓形成,在3h、6h、9h、12h、1d不同的时间点对大鼠静脉注射3种产地的降纤酶8U/kg,对照组注射等容生理盐水,观察2d,对大鼠进行行为学评分、MCA血流测定、梗死灶体积测定、病理改变及出血情况观察.结果降纤酶组3小时以内的血栓全部溶解,6小时内的部分溶解.降纤酶组各时间点无论血栓溶解与否,大鼠的行为学评分、梗死灶体积均较生理盐水组低,梗死灶周围微血管闭塞较生理盐水组少.但在降纤酶组中有2例发生出血,分别发生于血栓后6h、12h用药组.结论降纤酶对6小时以内的血栓有溶栓作用,对3小时以内的血栓溶解率最高.降纤酶除溶栓作用外,还可减少梗死灶体积,抑制微血管的血栓形成,改善微循环,改善卒中的预后.与其他溶栓剂相比并不增加出血并发症的发生.     

巴曲酶治疗急性缺血性脑卒中的疗效观察

目的:探讨巴曲酶对急性缺血性脑卒中的治疗效果。方法:选取60例发病在72h内的缺血性脑卒中患者,随机分为治疗组和对照组,治疗14d,观察血浆纤维蛋白的原变化,并评定临床治疗效果。结果:早期应用巴曲酶能降低血浆纤维蛋白原水平,提高治疗效果。结论:巴曲酶治疗急性缺血性脑卒中,安全有效,无明显毒副作用。     

降纤酶对实验性脑梗死灶周围微血管作用的观察

目的研究降纤酶对实验性脑梗死灶周围微血管的作用。方法用线栓法将易卒中型肾血管性高血压大鼠(stroke-pronerenovascularhypertensiverats,RHRSP)复制成一侧大脑中动脉闭塞(MCAO)模型,静脉注射降纤酶,对照组注射生理盐水,分别于缺血3、6、24h进行功能评分并处死大鼠,TTC染色计算脑梗死范围,HE染色观察梗死边缘区的病理形态,同时免疫组织化学检测尿激酶型纤溶酶原激活剂(urokinasetypeplasminogenactivator,uPA)和纤溶酶原激活剂抑制物1(plasminogenactivatorinhibitor1,PAI1)蛋白的表达。结果降纤酶能改善MCAO后神经功能评分,减少梗死灶体积,梗死灶边缘微血管损害减轻,血管内皮uPA蛋白表达减少及PAI1蛋白表达增加。结论降纤酶可能是通过抑制微血管内皮细胞uPA蛋白表达和增加PAI1蛋白表达而减轻脑梗死灶边缘微血管损害。     

易卒中型肾血管性高血压大鼠脑微血管超微结构观察

动态观察了易卒中型肾血管性高血压大鼠在高血压不同时期和卒中急性期的脑微血管病变。发现高血压早期已有脑微血管损害,并随血压升高和持续时间延长而加重,至高血压晚期出现管腔狭窄,内皮细胞水肿。此时虽未发生卒中,但受损微血管周围的神经细胞已出现线粒体肿胀,内质网扩张等缺血缺氧表现。卒中时,管壁结构严重破坏,有的管腔闭塞。显示高血压时脑微血管病变在高血压动脉硬化性卒中发病中起重要作用。     

巴曲酶联合依达拉奉治疗急性缺血性脑卒中疗效观察

目的研究巴曲酶联合依达拉奉对急性缺血性脑卒中的疗效。方法选取50例发病在72 h内缺血性脑卒中患者,随机分为治疗组和对照组,观察血浆纤维蛋白原的变化并评定临床治疗效果。结果巴曲酶和依达拉奉联合应用,疗效明显。结论巴曲酶联合依达拉奉治缺血性脑卒中,疗效显著,无明显不良反应。     

巴曲酶体外清除超氧自由基的研究

目的研究巴曲酶是否是真正直接的自由基清除剂。方法超氧自由基由邻苯三酚自氧化体系产生，在该体系中加入不同剂量的巴曲酶，然后记录自氧化曲线，巴曲酶清除氧自由基的作用可通过计算邻苯三酚自氧化抑制率得出。同时，测定邻苯三酚自氧化的耗氧率，间接证明巴曲酶的直接清除自由基作用。结果巴曲酶能明显抑制邻苯三酚自氧化，并能降低邻苯三酚自氧化的耗氧量。研究中还发现巴曲酶热稳定性强。结论巴曲酶是一种有效的超氧阴离子自由基清除剂，它对脑缺血／再灌注后脑损伤有保护作用     

巴曲酶治疗进展性脑梗死的血液流变学及疗效观察

目的评价巴曲酶(DF-521)治疗进展性脑梗死的血液流变学变化及临床疗效、安全性观察。方法采用随机分组、安慰剂对照方式分为试验组及对照组,2组均采用丹参注射液作为基础治疗,试验组采用巴曲酶(DF-521)注射液静滴,对照组加安慰剂静滴,均为隔日1次,共3次,同时对治疗组血液流变学进行动态观察。结果巴曲酶(DF-521)能改善血液流变学的某些因素,对血小板数、出凝血时间、肝肾功能无不良影响。试验组疗效明显优于对照组。结论巴曲酶(DF-521)治疗进展性脑梗死疗效肯定,而且安全性高、不良反应少,宜于早期应用。     

自由基清除剂联合巴曲酶治疗椎基底动脉系统进展型卒中

目的 评价新型自由基清除剂依达拉奉联合巴曲酶治疗椎基底动脉系统进展型卒中的有效性和安全性.方法 选择发病72h内的椎基底动脉系统进展型卒中患者76例,随机分为联合组和巴曲酶组,2组均采用巴曲酶注射液(10BU、5BU、5BU)静滴,隔日1次,共3次.联合组加用依达拉奉注射液30mg静滴,2次/d,共14d;巴曲酶组用等量生理盐水代替依达拉奉.2组病人分别在治疗前后定期进行神经功能缺损评分(NDS)并进行比较.结果 联合组临床显效率(63.16%)明显优于巴曲酶组(39.47%)(P＜0.01);2组均无明显不良反应.结论 依达拉奉联合巴曲酶治疗椎基底动脉系统进展型卒中安全有效.     

Fluctuation of serum NO(x) concentration at stroke onset in a rat spontaneous stroke model (M-SHRSP). Peroxynitrite formation in brain lesions

Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) develop hypertension and stroke at earlier ages than do nonmalignant SHRSP. Our previous findings suggested that reactive oxygen species were involved in the development of stroke in this strain. Nitric oxide (NO) which is more released at ischemia, might play a crucial role in stroke development by producing peroxynitrite, a neurotoxic substance. This study investigated whether the development of cerebrovascular lesion in M-SHRSP could be assessed by the fluctuation of serum NO(x) concentration, and whether peroxynitrite is associated with brain damage. Serum NO(x) levels were examined using an automated NO detector. Stroke-onset was temporally assessed according to a known method: changes in body weight, water intake, and neurologic symptoms. Cerebral lesions were confirmed by magnetic resonance imaging (MRI), and Evans blue extravasation at autopsy. MRI taken just after estimated stroke onset disclosed brain lesions. The baseline serum NO(x) level remained at 15-18 micromol/l, but the level gradually increased prior to stroke, and significantly at stroke onset. A marked rise in serum NO(x) occurred subsequently at poststroke. Immunohistochemical staining of nitrotyrosine, a peroxynitrite marker, was detected around vessels, neuronal cells and parenchyma in cerebral lesions. Stroke occurred in 50% of male M-SHRSP at 80 days of age. In conclusion, this study provides the first evidence for fluctuation of serum NO(x) at the onset of spontaneous stroke accompanying the appearance of peroxynitrite in brain lesions. Monitoring serum NO(x) would serve to assess the development of brain lesions at least in spontaneous stroke model.     

磁共振弥散/灌注加权成像确认局灶脑缺血半暗带的实验研究

目的　探讨超急性期确认局灶脑缺血半暗带的范围和演变规律。方法　用易卒中型肾血管性高血压大鼠(RHRSP)行左侧腔内线栓MCAO术 ,分别在闭塞 12h内的不同时间点及再灌注 48h后行T2 加权成像 (T2 WI)、磁共振弥散加权成像 (DWI)和磁共振灌注加权成像 (PWI)。将大鼠处死后行TTC染色 ,比较在闭塞不同的时间点上在两次T2 WI和DWI上病灶的演变和TTC染色上梗死灶的改变。结果　DWI在闭塞 30min时显示出确切的病灶 ,而T2 WI要在 3h以后才能显示出病灶 ;自 30min至 6h ,DWI所显示的病灶持续扩大 ,可逆性部分占首次DWI上病灶的百分比 (%RP)逐渐缩小 ,最终为负数 ;PWI在MCAO闭塞的即刻即在时间 信号强度曲线上表现为最大下降幅度的减小 ,复通后上升 5 0 %以上 ;半暗带部分水的表面弥散系数值 (ADC)为 (0 5 6± 0 0 2 )× 10 -5cm2 /s。结论　DWI能在超急性期 (3h以内 )显示出缺血病灶 ,根据梗死中心和梗死周边的ADC值的不同可以分辨出可逆性和不可逆性损伤的缺血组织 ;本模型的缺血半暗带存在的时间为6h。     

Nerve cell injury in the brain of stroke-prone spontaneously hypertensive rats

Summary The brain lesions in stroke-prone spontaneously hypertensive rats (SHRSP) are characterized by multifocal microvascular and spongy-cystic parenchymal alterations particularly in the gray matter. An essential feature of the lesions is the presence of edema with massive extravasation of plasma constituents as evidenced by specific gravity measurements, Evans blue technique and immunohistochemistry. The nerve cell injury occurring in the brain lesions in SHRSP is further characterized by light and electron microscopy in the present study. Two types of neuronal changes were seen within the blood-brain barrier (BBB) leakage sites. A small number of neurons with dark condensed nucleus and cytoplasm were found most often at the periphery of recent lesions. The majority of injured neurons were pale and showed intracellular edema confined to the dendrites and perikarya sparing axons and synapses. Their nuclei were weli preserved with finely dispersed chromatin. The swollen and watery cell processes of neurons and astrocytes gave a spongy appearance to the neuropil. The intracellular edema seemed to result in cytolysis. The results suggest that primary anoxiaischemia is not the major pathogenetic mechanism behind the nerve cell injury in severely hypertensive SHRSP, rather it is the massive BBB leakage and consequent brain edema that causes cytolytic destruction of neurons. Secondary focal ischemia as a consequence of occlusion in microvessels may, however, contribute to the nerve cell destruction.Supported by the Swedish Medical Research Council (Projects 12P-6827, 14X-4968, 12X-6238, 12X-7123 and 12X-3020), the Swedish National Association against Heart and Chest Diseases, the Medical Faculty, University of Lund, the MS-fund, Elsa Schmitz' Fund for Neurological and Neurosurgical Research and the Finnish Medical Research Council     

Cyst formation and glial response in the brain lesions of stroke-prone spontaneously hypertensive rats

Summary The brain lesions in spontaneously hypertensive stroke-prone rats (SHRSP) are characterised by multifocal microvascular damage, breakdown of the blood-brain barrier, massive extravasation of plasma constitutents and severe brain oedema, with consequent spongy and cystic tissue destruction in the cerebral cortex and basal ganglia as well as loosening of the white matter. In this paper we analyse in greater detail the pathogenetic mechanisms by which the spongy and cystic lesions are formed and the response of astrocytic cells. For this purpose, tracer (Evans blue)-stained brain lesions were examined in 8-month-old SHRSP immunohistochemically and electron microscopically. Sponginess of the neuropil in small lesions and at the periphery of larger lesions was due to swollen neuronal and astrocytic cell processes, i.e.at this stage the oedema was mainly intracellular. Cystic lesions were formed in the grey matter both by expansion of the extracellular space (ECS) containing protein-rich ocdema fluid, and by rupture and subsequent loss of massively swollen cellular elements. In the white matter small slit-formed cysts along the fibre tracts were also formed by the expansion of ECS. In apparently recent lesions astrocytes displayed cytoplasmic oedema but otherwise were still fairly normal. In more chronic lesions increased numbers of enlarged astrocytes with prominent staining for glial fibrillary acidic protein were present. Their distribution corresponded well to the spread ofoedema, i.e. they were prominent around the leaky vessels in the grey matter, in the subpial zone and in the white matter. In the reparative phase the grey matter cysts became lined by astrocytic processes, a new glia limitans. Profuse sheets of glial processes in the neuropil around the cysts reestablished the compactness of the brain parenchyma.Supported by the Swedish Medical Research Council (Projects 12P-6827, 14X-4968, 12X-07123, and 12X-03020), the Finnish Medical Research Council, the Swedish National Association against Heart and Chest Diseases, the Medical Faculty, University of Lund and the MS-Fund     

肾血管性高血压大鼠脑梗塞后脑微血管形态计量学动态观察

本研究选用双肾双夹肾动脉狭窄术复制成的肾血管性高血压大鼠（ＲＨＲ）５４只；同龄正常血压鼠（ＳＤＲ）５４只，各分为大脑中动脉闭塞（ＭＣＡｏ）前、后不同时间的９个实验和对照组，各组均即时从心腔等压灌注中华墨汁，取脑顶叶梗塞灶边缘区，行冠状、矢状、水平三方向取材，制片，在显微镜下作微血管形态计量学测定．结果显示ＲＨＲ顶叶脑皮质毛细血管直径、单位体积毛细血管长度、表面积、通过２００μｍ的毛细血管支数均较ＳＤＲ减少，表明高血压可致脑微血管稀疏；同时观察到局部脑梗塞后上述反映毛细血管网三维构筑的参数变化远较对照鼠明显，缺血后脑损伤更严重。说明毛细血管损伤程度与梗塞灶的大小直接相关，因此应加强高血压的防治，以保护脑微血管立体构筑。