大鼠脑缺血再灌注区ICAM—1的表达与粘附性变化的实验研究

目的:观察大鼠脑缺血再灌注后缺血区ＩＣＡＭ－１ｍＲＮＡ和蛋白的表达及白细胞和血管内皮细胞间粘附性的变化。方法:４０只Ｗｉｓｔａｒ大鼠分为正常组、假手术组和缺血２ｈ再灌注２、４、１２、２４、４８、９６ｈ组,原位杂交和兔疫组化法检测ＩＣＡＭ、１ ｍＲＮＡ和蛋白表达,超高速摄录像系统观察缺血区微血管内白细胞与内皮细胞间的粘附性变化。结果:缺血再灌注后局部脑组织ＩＣＡＭ－１ｍＲＮＡ和蛋白的表达以及微动脉内白细胞与内皮细胞间粘附性均明显增高。结论:脑缺血再灌注后ＩＣＡＭ－１表达增高,介导了白细胞与血管内皮细胞间的粘附增强,参与了缺血再灌注损伤。     

不透X线的水凝胶微球的远期栓塞效果及生物相容性研究

一、实验材料与方法健康家兔24只,雌雄不限;体重25～30ｋｇ;随机分为三组,每组8只,在ＤＳＡ透视下分别采用250～300μｍ的国产水凝胶微球(ＨＭｓ)、进口ＨＭｓ、进口ＰＶＡ选择性经兔右侧颈内动脉(ＩＣＡ)、颈外动脉(ＥＣＡ)分支栓塞,每组2只栓塞ＩＣＡ,6只栓塞ＥＣＡ分支。栓塞后观察动物神经功能变化,6月后再次经兔右颈动脉造影,了解栓塞血管有无再通,并取栓塞血管进行光镜、电镜观察。二、实验结果三组动物ＩＣＡ栓塞后可出现呼吸困难、抽搐及偏瘫,于1/2小时内死亡4只,3天内死亡2只。选择性ＥＣＡ分支栓塞后,三组动物全部存活,平均体重增…     

小脑梗塞的临床及MRI诊断分析

本文报告１２例小脑梗塞的ＭＲＩ检查，并与ＣＴ和临床检查对照。讨论了其病因、分型、ＭＲＩ平扫及Ｇｄ—ＤＴＰＡ增强所见，诊断和治疗。在小脑梗塞刀性期，Ｔ１加权像（Ｔ１Ｗ１）呈等信号或稍低信号，Ｔ２Ｗ１呈高信号。Ｇｄ—ＤＴＰＡ增强扫描及复查扫描对小脑梗塞与肿瘤的鉴别有重要意义。大面积小脑梗塞如能早期确诊仍可行保守治疗。     

弹力酶诱导的兔囊状动脉瘤早期形态学研究

目的研究猪胰弹力酶诱导的兔囊状动脉瘤的早期形态学及病理学变化特征.方法使用35只新西兰大白兔制作猪胰弹力酶诱导的囊性动脉瘤模型后,在第3、7、14、21、30天通过静脉血管造影观察动脉瘤模型的形态学动态变化特征及动脉瘤管腔内形态变化特征.结果静脉血管造影显示:术后第3、7、14、21天平均瘤颈、瘤高及瘤宽不断增大;术后第30天瘤颈、瘤高及瘤宽无明显增大.整体标本观察可见术后3d瘤腔内主要为血栓填充;术后7d瘤腔内血栓减少,瘤腔顶部血栓出现完整纤维膜;术后14～30d,瘤腔顶部血栓逐渐机化.结论猪胰弹力酶诱导的兔动脉瘤腔内最初主要为血栓填充,随后血栓逐渐机化,瘤腔不断增大,在21d左右形态趋于稳定.     

建立椎管内静脉高压动物模型的手术方法及稳定性评价*

背景：构建稳定的脊髓静脉高压动物模型可为临床研究脊髓血管病变提供可靠的平台,课题组前期已成功构建了兔脊髓静脉高压模型。 目的：在前期研究基础上改进手术方法和围手术期处理,建立长期稳定的兔脊髓静脉高压模型。 方法：48只新西兰大白兔随机分为急性期组、短期组、中期组、长期组,每组12只兔又分为模型兔8只和假手术兔4只。模型兔通过开腹侧侧吻合兔左肾动静脉,形成动静脉瘘,结扎后腔静脉远端和近端导致动脉血异常引流至腰静脉、椎管内静脉丛形成脊髓淤血和脊髓静脉高压。采用Jacobs法对后肢功能评级,Reuter法评估脊髓感觉运动反射功能,每组动物到期后对模型兔行MRI扫描、经股动脉DSA检查动静脉瘘口的通畅,并灌注解剖取脊髓行病理学检查以判定模型符合要求。 结果与结论：32只模型兔存活29只,生存率91%,动静脉瘘口通畅率79%,但长期组瘘口通畅率低,仅29%。术后模型后肢运动、感觉功能均有所减退。模型兔脊髓MRI表现为脊髓相应阶段的水肿;病理检查在光镜下见脊髓实质内淋巴细胞的浸润、胶质细胞的增生、髓内血管的玻璃样变性和神经元细胞变性,符合脊髓静脉高压的脊髓病理变化;透射电镜观察可见髓鞘板层的松散、薄髓纤维内线粒体数目增加和神经元的固缩。提示成功建立模拟人类脊髓血管畸形的脊髓静脉高压机制导致脊髓损伤的动物模型,该模型的可靠性和稳定性较高。     

巨大脊髓血管畸形一例

患者　男,28岁。因双下肢进行性无力伴疼痛1年,加重5个月入院。查体:双下肢痛、触觉减退。会阴部及马鞍区痛、触觉存在。左下肢肌力Ⅲ级,右下肢肌力Ⅱ～Ⅲ级。双下肢肌张力稍低。提睾及肛门反射减退。双膝反射未引出。胸、腰椎正、侧位Ｘ线平片显示Ｔ9～12左侧椎旁软组织增宽。腰椎生理曲度变直。ＭＲＩ结果:Ｔ7～Ｌ3椎体平面Ｔ1ＷＩ、Ｔ2ＷＩ平扫及ＧｄＤＴＰＡ增强扫描显示Ｔ7～Ｌ3椎体平面之椎管内蛛网膜下腔及脊髓表面可见许多散在较小血管流空信号及小点状等Ｔ1长Ｔ2信号灶。注射ＧｄＤＴＰＡ后,脊髓表面及蛛网膜下腔内有许多散在点状…     

兔颈总动脉侧壁型动脉瘤模型的建立

目的 建立类似人颅内动脉瘤特点的兔颈总动脉侧壁型动脉瘤模型.方法 切取兔左颈总动脉约8mm,经弹性蛋白酶和胶原酶处理后,采用端侧吻合法将其吻合到右颈总动脉,建立侧壁型动脉瘤20只.术后分别行彩色多普勒检查、DSA和动脉瘤壁病理检查.结果 本组建立兔颈部囊状动脉瘤模型20只,术后健康成活18只,动脉瘤自发破裂导致死亡2只.DSA显示:动脉瘤与载瘤动脉通畅16只,动脉瘤腔自发性完全闭塞2只;造模成功率为80％.彩色多普勒发现:动脉瘤模型建立后即刻平均直径为(2.57±0.20) mm,2周后平均直径为(3.14±0.20) mm,两者差异有统计学意义(P＜0.05);且载瘤动脉血流速度较动脉瘤内血流速度快.病理检查显示:动脉瘤模型的动脉壁内弹力层和中弹力层基本消失.结论 经弹性蛋白酶和胶原酶处理的兔颈总动脉侧壁型动脉瘤模型,在形态结构、组织结构、自然发展史及血流动力学特点上与人颅内动脉瘤相似,是模拟人颅内动脉瘤的最佳模型之一.     

33例椎-基底动脉瘤的临床观察

目的：探讨椎－基底动脉瘤治疗方法与预后关系。材料与方法：报告３３例椎－基底动脉瘤。动脉瘤破裂致ＳＡＨ１８例，动脉瘤直径从５ｍｍ到４５ｍｍ。其中９例行保守治疗。直接手术治疗中，９例夹闭术，２例瘤壁加固术。１３例行血管内栓塞治疗。结果：９例保守治疗中３例因再次出血死亡。１１例直接手术均痊愈。１３例血管内栓塞治疗后１～３个月后复查造影，闭塞率＞８０％者１２例。结论：椎－基底动脉瘤积极手术治疗可降低死亡率，依动脉瘤部位与大小采用不同手术入路至关重要，血管内栓塞治疗适于直接手术难以达到者，疗效肯定。     

一种新的蛛网膜下腔出血动物模型制作方法

目的 建立一种能更接近人脑动脉瘤破裂引起蛛网膜下腔出血(SAH)过程的动物模型.方法 通过介入法经股动脉路径穿刺兔颈内动脉,造成SAH,然后将60只实验兔按各时间点(对照组、假手术组、术后0h、3h、6h、12 h、1d、3d、7d、14 d)分成10组,每组6只,行脑血管造影,然后灌注-固定,处死后取基底动脉切片行HE染色观察,通过图像分析系统,测定动脉内径和血管壁厚度.结果 血管内穿刺法制作兔的SAH模型呈急性期脑血管痉挛(SAH后12 h)和迟发性脑血管痉挛(SAH后7d)双相改变.结论 此动物模型能较好地模拟动脉瘤性SAH后血管痉挛改变的病理过程.     

栓线法大鼠局灶性脑缺血模型的研究

采用颈部旁侧手术入路，结扎右侧颈总动脉、颈外动脉及其分支后颈内动脉栓线法制作大鼠大脑中动脉闭塞再灌流损伤模型。闭塞成功率９４．１％，动物偏瘫症状评分在缺血２ｈ再灌流３ｄ后趋于稳定，病理改变以尾壳核损害最重。再灌流７ｄ脑梗塞体积为９７．８±９．４ｍｍ３，动物死亡率５９．４％。缺血２ｈ后再灌流先出现过渡灌注，而后呈持续性低灌注。本文模型勿需开颅，缺血效果可靠，对局灶性脑缺血的研究具有实用价值。     

经股动脉入路建立球囊损伤兔颈动脉狭窄模型

目的经股动脉入路制作一种实用、可靠且稳定的颈动脉狭窄模型,用于探讨颈动脉再狭窄的防治。方法新西兰大白兔20只,随机分为对照组、实验1周组、实验2周组和实验4周组,每组5只,常规喂养。所有动物采用经右侧股动脉入路置入HyperForm球囊,实验组行右颈总动脉定比扩张,对照组行单纯右颈动脉路图显示,术后以普通饮食喂养。实验1、2、4周组实验兔分别于手术后1周、2周和4周处死,并在第4周同时处死对照组兔。右颈动脉分叉近心端1～2cm节段取材送光镜和电镜检查,分别观察血管壁增生情况并计算血管内膜和中膜厚度。结果与对照组比,实验组新生内膜厚度呈持续性显著增加(P<0.01),实验2周组与实验1周组比较及实验4周组与实验2周组相比,内膜厚度均显著增加(P<0.01)。各组中膜厚度未见明显统计学差异(P>0.05)。结论经股动脉入路用Hyper Form球囊行颈动脉定比扩张能成功地制作一种稳定、简便可靠的颈动脉狭窄动物实验模型。血管平滑肌细胞的过度增生是造成PTA术后管腔再狭窄的主要因素。     

A modified rabbit model of carotid atherosclerotic plaque suitable for the stroke study and MRI evaluation

In order to induce a modified rabbit model of carotid atherosclerotic plaque suitable for the stroke study and to evaluate the lesion with magnetic resonance imaging (MRI). Eight rabbits of group A were fed with high-fat diet only. Atherosclerosis at the right common carotid artery was induced in rabbits of group B (n = 12) by high-fat diet and balloon catheter injury to the endothelium 4 weeks later. The rabbits were examined in vivo with a 1.5-T MRI. After 4 weeks on the high-fat diet, the serum lipid levels were markedly increased, which became significantly higher than the baseline levels. The lesions on both MRI and histology were remarkable. One week after balloon injury, the signal of injured right common carotid was higher on all the contrast-weighted images than the left side. The extent of abnormal signal was reduced 9 weeks after balloon injury. Hemorrhage was detected on all the contrast-weighted images. In conclusion, the rabbit model established by the authors is such a feasible one to the study of stroke caused by carotid atherosclerosis.     

Early partial reperfusion in a new rat model of focal cerebral ischaemia

The influence of early partial reperfusion in a new rat model of focal cerebral ischaemia was investigated. Two groups, each of 30 adult male rats, were subjected to permanent occlusion of the right middle cerebral artery. The former, (group A) had an additional permanent occlusion of both common carotid arteries; the latter (group B) had a temporary carotid occlusion lasting for two hours. Mortality rate, evaluated within three days, was 70% ingroup A and 20% in group B. The mean size of cerebral infarcts was 63% in group A whereas it was 21% in group B. These data suggest that, in this animal model, early partial reperfusion is effective in reducing the mortality rate, and the size of the cerebral infarcts. Furthermore, this experimental model appears suitable for studies elucidating the role of reperfusion andlor other efforts in focal cerebral ischaemia.     

颈动脉粥样硬化斑块CD147、MMP-9表达及阿托伐他汀干预的影响

目的 探讨兔颈动脉粥样硬化斑块中CD147、基质金属蛋白酶-9(MMP-9)的表达情况以及阿托伐他汀对其表达的影响.方法 24只新西兰大白兔按随机数字表法分为3组:正常对照组8只,普通饲料喂养16周;余16只给予球囊损伤颈总动脉+高胆固醇喂养,12周后分成模型对照组和阿托伐他汀组(每天2.5 mg/kg阿托伐他汀灌胃),继续喂养4周后给予鲁塞尔氏蛙蛇毒和组胺触发斑块破裂.对斑块进行病理分析,免疫组织化学法检测斑块内巨噬细胞及CD147、MMP-9蛋白表达,逆转录聚合酶链反应(RT-PCR)检测斑块内CD147、MMP-9mRNA表达.结果 药物触发后模型对照组存活的6只兔中有4只发生斑块破裂及血栓形成,阿托伐他汀组存活的7只兔中有1只发生斑块破裂及血栓形成,正常对照组中未见斑块破裂及血栓形成.与模型对照组比较,阿托伐他汀组斑块内巨噬细胞含量明显减少(33.62±3.82vs16.22±2.61),CD147蛋白表达的阳性染色面积比明显降低(29.54±3.03vs14.22±1.63),MMP-9蛋白表达的阳性染色面积比明显降低(21.18±4.75 vs 11.11±1.87),差异有统计学意义(P＜0.05＝.模型对照组和阿托伐他汀组斑块内CD147 mRNA表达水平分别为0.939±0.105和0.426±0.112,MMP-9 mRNA表达水平分别为0.335±0.069和0.135±0.067,比较差异有统计学意义(P＜0.05＝.Pearson相关检验显示斑块中MMP-9蛋白与CD147蛋白表达呈正相关(r=0.669,P=0.001),MMP-9 mRNA与CD147 mRNA表达呈强正相关(r=0.783,P=0.000).结论 CD147、MMP-9表达上调可能参与斑块不稳定的发生机制,阿托伐他汀可能通过下调CD147、MMP-9的表达发挥稳定斑块的作用.     

预防及超早期应用尼莫同对小鼠局灶性脑梗死的影响

目的观察尼莫同超早期给药对小鼠局灶性脑梗死的影响.方法经右侧颈总动脉将尼龙单丝线栓至大脑中动脉造成永久性缺血模型.经尾静脉及腹腔注射尼莫同,TTC染色、图像分析仪测定脑梗死体积.结果单纯缺血组各时间点脑梗死体积最大,缺血前预防给药组各时间点脑梗死体积最小,缺血后即刻给药组各时间点脑梗死体积介于二者之间.结论小鼠大脑中动脉闭塞后其局灶性脑梗死体积于术后第3天达高峰.缺血前预防给药组、缺血后即刻给药,尼莫同均可使梗死体积减少.     

Intracarotid abciximab injection to abort impending ischemic stroke during carotid angioplasty

BACKGROUND: Abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist, prevents ischemic complications during percutaneous transluminal coronary angioplasty and was recently shown to open occluded vessels in patients with acute myocardial infarction when used alone or in combination with other thrombolytic agents. In an animal model of arterial thrombosis, abciximab was found to be safe and effective for the prevention of carotid artery thrombosis. However, the safety and efficacy of abciximab in the treatment of acute ischemic cerebrovascular events is unknown at present. CASE DESCRIPTION: We describe 3 patients who experienced ischemic cerebrovascular events with symptoms involving the middle cerebral artery territory while undergoing percutaneous angioplasty and stenting to their internal carotid arteries. Abciximab was administered to each patient within 10 min of symptom onset as a bolus (0.25 mg/kg) into the ipsilateral common carotid artery followed by continuous intravenous infusion (9 microg/min) for 12 h. All patients' symptoms resolved completely (by 25 min, 40 min and 5 h, respectively) with no further neurological complications. CONCLUSIONS: Our preliminary observation suggests that abciximab may improve neurological outcome following middle cerebral artery ischemic events associated with carotid angioplasty and stenting. Large prospective studies are warranted to establish the safety and efficacy of abciximab in acute ischemic stroke, either as a primary treatment modality or an adjunct to carotid angioplasty and stenting.     

缺血缺氧性新生大鼠皮层神经元胞浆Smac/Diablo、caspase-9的表达及参附注射液的干预作用

目的 了解缺血缺氧性脑损伤(HIBD)新生大鼠神经元胞浆Smac/Diablo、caspase-9的变化及其相互关系,同时观察参附注射液的干预效果.方法 HIBD模型制作参照Rice等方法.新生7dSD大鼠按照完全随机数字表法分为假手术组、生理盐水对照组与参附治疗组,再按照造模后不同观察时间点又分为3 h、6 h、12 h、24 h、3 d、7 d6个亚组,每亚组8只.参附治疗组于造模后即刻腹腔注射参附注射液10 mL/kg,1次/d,连续用药3 d.生理盐水对照组用生理盐水替代参附注射液,用法用量相同;假手术组仅切开颈正中皮肤和分离右侧颈总动脉,不结扎,不缺氧.Western blotting检测各时间点各组大鼠神经元胞浆中Smac/Diablo、活化caspase-9蛋白的表达.结果 假手术组Smac/Diablo、caspase-9蛋白表达微弱.生理盐水对照组与参附治疗组2种蛋白造模后3 h即明显增加,与假手术组比较,差异有统计学意义(P＜0.05);24 h时2种蛋白表达达到峰值,3 d后明显下降,7 d时接近假手术组.其中参附治疗组Smac/Diablo蛋白表达量12 h、24 h、3 d、7 d时较生理盐水对照组明显下降,差异有统计学意义(P＜0.05);参附治疗组caspase-9蛋白12 h、24 h、3 d时较生理盐水对照组明显下降,差异有统计学意义(P＜0.05).结论 (1)HIBD新生大鼠脑皮层神经元存在Smac/Diablo蛋白胞浆转位,同时伴有胞浆活化caspase-9表达增加:参附可减少HIBD大鼠Smac/Diablo蛋白的胞浆转位,减少caspase-9的活化.(2)Smac/Diablo、caspase-9参与了HIBD新生大鼠迟发性神经元损伤的病理机制.

Abstract：

Objective To investigate the expressions of Smac/Diablo and caspase-9 and their corelations in the cytoplasm of cerebral cortex of neonatal rats with hypoxic-ischemic brain damage (HIBD), and the possible interference effects of Shenfu injection on them. Methods Postnatal 7-d SD rats were randomly divided into Shenfu treatment group (group SF), normal saline group (group C) and sham-operated group (group S). Rat models of HIBD were established according to Rice's method.Based on the observing times after the success of model making, each group (n=48) was equally divided into 6 subgroups (3, 6, 12 and 24 h, and 3 and 7 d observing groups). Rats in the group S were not performed ligation of the right common carotid artery and not underwent hypoxia but only performed the separation of right common carotid artery. Shenfu injection was administered by intraperitioneal injection right after H/I insult and then once daily at a dosage of 10 mL/kg for 3 d into the rats of group SF. Saline was also administered into the rats of group C by the same methods and at the same dosage. Cytoplasm proteins were extracted from the cerebral cortex tissue, and then, Western blotting was employed to detect the protein levels of Smac/Diablo and activated caspase-9 in cytoplasm. Results Western blotting showed that the expression levels of Smac/Diablo and activated caspase-9 in cytoplasm of group S were very low; the expression levels of Smac/Diablo and activated caspase-9 in cytoplasm of group SF and group C were increased markedly since the 3rd h of the success of model making as compared with those in group S (P＜0.05): these in the 2 groups reached their peak levels 24 h after H/I insult, gradually decreased 3 d after H/I insult, and almost returned to the original levels 7 d after H/I insult. The expressions of Smac/Diablo in cytoplasm of group SF 12, 24 h and 3 d after H/I insult was significantly lower than that of group C (P＜0.05); the expression of activated caspase-9 in cytoplasm of group SF 12,24 h and 3 d after H/I insult was significantly decreased as compared with that of group C (P＜0.05).Conclusion Smac/Diablo cytoplasm translocation and increased expression level of caspase-9 appear in the cytoplasm of cerebral cortex cells after H/I injury; Shenfu injection can inhibit the expressions of Smac/Diablo and caspase-9; Smac/Diablo and caspase-9 involve in the pathophysiological mechanisms of neuronal damage after H/I.     

Early partial reperfusion in a new rat model of focal cerebral ischaemia

The influence of early partial reperfusion in a new rat model of focal cerebral ischaemia was investigated. Two groups, each of 30 adult male rats, were subjected to permanent occlusion of the right middle cerebral artery. The former, (group A) had an additional permanent occlusion of both common carotid arteries; the latter (group B) had a temporary carotid occlusion lasting for two hours. Mortality rate, evaluated within three days, was 70% in group A and 20% in group B. The mean size of cerebral infarcts was 63% in group A whereas it was 21% in group B. These data suggest that, in this animal model, early partial reperfusion is effective in reducing the mortality rate, and the size of the cerebral infarcts. Furthermore, this experimental model appears suitable for studies elucidating the role of reperfusion and/or other efforts in focal cerebral ischaemia.     

改良的胰弹性蛋白酶诱导兔囊状动脉瘤模型

目的 通过简单手术方法建立形态学和组织学上类似人颅内囊状动脉瘤的动脉瘤模型.方法 第一组采用弧形动脉瘤夹临时夹在兔右颈总动脉起始部及部分右锁骨下动脉上,向动脉残腔内注入猪胰弹性蛋白酶溶液消化20 min;第二组使用生理盐水代替胰弹性蛋白酶;第三组弧形动脉瘤夹夹在右颈总动脉起始部上3 mm,胰弹性蛋白酶诱导.结果 第一组成功建立动脉瘤模型,病理显示瘤壁完全缺失弹力层,术后6个月内各观察时期动脉瘤大小差异无统计学意义(P＞0.05).第二组和第三组造影检查均形成残端.结论 胰弹性蛋白酶和动脉瘤夹的位置是决定该模型成功的关键.