颅内囊性动脉瘤瘤壁的组织结构变化及其临床意义

目的观察颅内囊性动脉瘤瘤壁超微病理性结构,预测颅内囊性动脉瘤进展。方法在光学显微镜及电子显微镜下观察12例颅内多发动脉瘤（19个标本）、15例单发动脉瘤及9例重型颅脑损伤患者（对照组）脑血管标本的血管壁组织结构。同时采用免疫组化方法检测各组血管壁标本中的Ⅳ型胶原表达情况。结果在动脉瘤标本中可见动脉瘤壁的内皮细胞损伤、弹力板不完整或缺失及平滑肌细胞坏死,与正常大脑中动脉动脉壁有明显的差异;动脉瘤壁Ⅳ型胶原表达较对照组显著减低（P〈0.05）。结论颅内囊性动脉瘤壁中各层结构的形态及分布特点与正常大脑中动脉动脉壁存在较大差异,这可能是颅内囊性动脉瘤容易破裂的原因。     

单核细胞趋化蛋白-1在颅内动脉瘤壁的表达

目的 研究内皮细胞单核细胞趋化蛋白-1（monocyte chemotactic protein 1,MCP-1）在颅内动脉瘤壁的表达及其在炎症反应过程中的作用。方法 天坛医院2006年10月至2007年9月术中随机取得9例颅内动脉瘤,以同期5例脑肿瘤患者的颞浅动脉为对照,通过苏木素-伊红（hematoxylin and eosin,HE）染色及Western-blot方法研究MCP-1在颅内动脉瘤发生中所起的作用。结果 HE染色显示,相对于正常动脉壁,动脉瘤其内层、外层网架结构均有破坏;Western-blot显示,MCP-1在动脉瘤中的蛋白表达明显增高。结论 MCP-1在囊性动脉瘤壁中的高表达与动脉瘤的发展有相关性。通过某些途径阻断炎性反应的过程可能防止囊性动脉瘤的形成。     

颅内动脉瘤的MMP-9及超微结构研究

目的探讨基质金属蛋白酶9（MMP-9）对脑血管壁细胞外基质（ECM）破坏在颅内动脉瘤发病机制中的作用。方法对15例颅内动脉瘤标本和6例非脑血管病病人的正常脑血管．应用实时荧光定量PCR检测脑血管壁组织内MMP-9 mRNA的基因表达水平，并通过电镜观察颅内动脉瘤病人血管壁细胞及ECM的形态学变化。结果动脉瘤壁组织中MMP-9mRNA的表达是正常脑血管的10．06倍（P〈0．01）。电镜下见动脉瘤壁内皮细胞损伤，中层平滑肌细胞数目明显减少并呈凋亡状态．ECM严重破坏：而正常脑血管壁细胞及基质纤维清晰可见，结构完整。结论颅内动脉瘤壁组织中MMP-9的基因表达水平显著升高，并可能通过破坏ECM和诱导平滑肌凋亡参与颅内动脉瘤的发病机制。     

基质金属蛋白酶-9和血管内皮生长因子在颅内动脉瘤中的表达

目的通过观察基质金属蛋白酶-9(MMP-9)和血管内皮生长因子(VEGF)在颅内动脉瘤中的表达情况,并且与正常脑动脉血管组织中两者的表达相比较,为研究动脉瘤的发病原因及机制提供线索。方法用免疫组织化学方法对16例经手术和病理证实的脑动脉瘤标本中的MMP-9、VEGF的表达进行检测,同时将7例颞叶癫痫间患者手术切除颞极的颞叶皮层动脉血管组织标本作为相对正常脑动脉血管组织的对照,进行MMP-9、VEGF的表达检测,将所得染色标本在光镜下观察,并用医学图像分析系统进行定量分析。结果7例正常脑动脉血管组织中无MMP-9、VEGF阳性表达,而动脉瘤的MMP-9、VEGF阳性表达率分别为81.2%(13/16)和87.5%(14/16),2组标本相对照具有显著差异(P<0.05);MMP9-在动脉瘤壁内、中、外膜中均有表达,其中外、中膜阳性表达较高;VEGF主要在动脉瘤壁中、外膜表达,而内膜表达较少。结论动脉瘤的发生、生长和破裂是个很复杂的过程,MMP-9及VEGF可能是主要的影响因素之一,两者可能与动脉瘤的发生,增长以及结构维持有关。     

c-Jun在颅内动脉瘤中的表达及对MMP-9表达调控作用的研究

目的检测c-Jun在颅内动脉瘤中的表达及探讨其对基质金属蛋白酶-9（MMP-91表达调控的意义。方法对15例颅内动脉瘤标本和6例非脑血管病患者的正常脑血管应用免疫组化SP法和实时荧光定量RT-PCR法分别检测脑血管壁组织内c-Jun免疫活性和MMP-9mRNA的表达水平。结果c-Jun免疫活性在颅内动脉瘤壁组织内为1．92±0．51，正常脑血管壁内为0．17±0．41，二者有显著性差异（P〈0．01）。动脉瘤壁组织中MMP-9mRNA的表达是正常血管的10．06倍（P〈0．01）。颅内动脉瘤壁组织内c-Jun的免疫活性和MMP-9mRNA的表达呈正相关（r=．818，P〈0．001）。结论活化后的c-Jun可能通过其结构域内MMP-9结合位点启动MMP-9大量转录而参与颅内动脉瘤的发病机制。     

破裂颅内动脉瘤瘤壁核因子κB与血管内皮生长因子的表达

目的 探讨核因子kB(NF-kB)和血管内皮生长因子(VEGF)在破裂颅内动脉瘤瘤壁的表达及相关性,并观察两者与瘤壁血管重塑的关系.方法 采用免疫组织化学方法对26例DSA和手术证实的颅内动脉瘤瘤壁标本的NF-kB和VEGF表达进行检测,10例因脑外伤手术切除颞极的颞叶皮层动脉血管标本作对照,光镜下观察各组染色结果并作统计学分析,同时行常规组织学检查观察瘤壁粥样硬化病变特点.结果 动脉瘤组标本NF-k＞B和VEGF阳性表达分别为23/26和21/26,10例正常对照组标本中NF-k＞B和VEGF仅有微弱表达,差异有统计学意义(P＜0.01); NF-kB和VEGF在颅内动脉瘤瘤壁中的表达均以内膜、中膜较高,外膜表达较少,两者在瘤壁中的表达有正相关性,相关系数为0.740.组织学检查发现瘤壁出现程度不同的动脉粥样硬化改变.结论 动脉粥样硬化是颅内动脉瘤伴随的重要病理改变.NF-kB和VEGF在颅内动脉瘤发病和粥样硬化病变过程中可能发挥了重要的协同作用.     

破裂颅内动脉瘤瘤壁核因子kB与血管内皮生长因子的表达

目的 探讨核因子kB(NF-kB)和血管内皮生长因子(VEGF)在破裂颅内动脉瘤瘤壁的表达及相关性,并观察两者与瘤壁血管重塑的关系.方法 采用免疫组织化学方法对26例DSA和手术证实的颅内动脉瘤瘤壁标本的NF-kB和VEGF表达进行检测,10例因脑外伤手术切除颞极的颞叶皮层动脉血管标本作对照,光镜下观察各组染色结果并作统计学分析,同时行常规组织学检查观察瘤壁粥样硬化病变特点.结果 动脉瘤组标本NF-k＞B和VEGF阳性表达分别为23/26和21/26,10例正常对照组标本中NF-k＞B和VEGF仅有微弱表达,差异有统计学意义(P＜0.01); NF-kB和VEGF在颅内动脉瘤瘤壁中的表达均以内膜、中膜较高,外膜表达较少,两者在瘤壁中的表达有正相关性,相关系数为0.740.组织学检查发现瘤壁出现程度不同的动脉粥样硬化改变.结论 动脉粥样硬化是颅内动脉瘤伴随的重要病理改变.NF-kB和VEGF在颅内动脉瘤发病和粥样硬化病变过程中可能发挥了重要的协同作用.     

亚低温对大鼠局灶性脑缺血再灌注后半暗带区iNOS诱导细胞凋亡的影响

目的通过研究亚低温对大鼠局灶性脑缺血再灌注后诱导型一氧化氮合酶（iNOS）表达和细胞凋亡的影响，探讨亚低温脑保护的可能机制。方法雄性SD大鼠54只随机分为假手术组、常温缺血组和亚低温组。线栓法制备大脑中动脉闭塞再灌注模型。于缺血后48h取脑组织，邻片行HE染色，检测各组不同脑区iNOS蛋白表达和细胞凋亡情况，免疫双重染色研究iNOS蛋白表达与细胞凋亡间的关系，同时行NO含量测定。结果常温缺血组皮质缺血半暗带（IP）区iNOS免疫反应较强，TUNEL阳性细胞也主要位于皮质IP区，免疫双重染色发现TUNEL阳性细胞中存在着iNOS蛋白表达。亚低温组IP区iNOS蛋白表达明显下调，NO产生减少．IP区细胞凋亡的数目也减少。结论亚低温可能通过抑制IP区iNOS蛋白表达，减少NO产生．阻遏细胞凋亡，从而起到脑保护作用。     

血管生长因子和结构蛋白在新疆哈萨克族破裂和未破裂颅内动脉瘤中的表达

目的 评价血管生长因子(VEGF,TGF -a)和结构蛋白(Ⅲ、Ⅳ型胶原,平滑肌肌动蛋白-a)在哈萨克族未破裂和破裂脑动脉瘤中的表达差异性,探讨脑动脉瘤生长和破裂的可能机制.方法 对12例哈萨克族多发脑动脉瘤患者术中同时获得的12对破裂与未破裂动脉瘤标本和尸体中所获得的5例正常脑动脉标本进行血管因子(VEGF和TGF-a)和结构蛋白(Ⅲ、Ⅳ型胶原,平滑肌肌动蛋白-a)进行免疫组化学染色.结果 VEGF在正常血管壁中无表达,在未破裂动脉瘤中表达较弱,而在破裂动脉瘤中表达较明显.TGF-a在正常血管壁中表达明显,在未破裂动脉瘤中表达较明显,而在破裂动脉瘤中表达较弱.Ⅲ、Ⅳ型胶原在正常血管壁中表达明显,而在未破裂动脉瘤中表达较明显,在破裂动脉瘤中表达较弱.SMC -a在正常动脉壁中表达明显,在未破裂动脉瘤中表达较明显,而在破裂动脉瘤中表达较弱.结论 血管生长因子的异常表达和血管壁基质结构蛋白的降解是脑动脉瘤形成与破裂的主要机制之一.     

颅内动脉瘤组织免疫和炎症相关差异表达基因的研究

目的检测颅内动脉瘤组织中的免疫和炎症相关差异表达基因,探讨其在颅内动脉瘤发病机制中的作用。方法利用Affymetrix公司的人类基因组基因芯片U133A分别检测3例颅内动脉瘤组织和3例正常颅内动脉组织中的基因表达谱,用生物信息学软件进行比较分析,对差异表达基因进行功能分类．对其中的免疫和炎症相关基因进行分析。结果与正常颅内动脉组织相比,在所检测的总共22215个基因中．颅内动脉瘤组织中差异表达水平达10倍以上的基因中,有40个基因与免疫和炎症有关．其中38个基因的表达水平在颅内动脉瘤中上调10倍以上,2个基因表达水平下调10倍以上。结论免疫和炎症相关基因的异常表达可能参与了颅内动脉瘤的形成和发展。     

Expressions of PDGF-B and collagen type III in the remodeling of experimental saccular aneurysm in rats

The essential etiologic factors of intracranial berry aneurysm may be the hemodynamic stress on the arterial wall. Vascular remodeling triggered by abnormal hemodynamic stress on the blood vessels may play an important role in the formation, development and rupture of intracranial aneurysms. However, the specific causative mechanisms associated with this remain elusive. In this study, we look for the possible mechanism of platelet-derived growth factor B (PDGF-B) on the pathogenesis of saccular aneurysms in rats. Direct microsurgical destruction of the arterial intima and internal elastic lamina at the bifurcation of the carotid artery was performed in 30 rats to induce saccular aneurysms and the contralateral carotid arteries were ligated in half of them. After 4-5 months, the size of the aneurysms was determined. The expressions of PDGF-B and collagen type III on the walls of the normal carotid arteries and the saccular aneurysms were determined by in situ hybridization and immunohistochemistry. Saccular aneurysms could be induced immediately by destroying the intima and internal elastic lamina at the bifurcation of the carotid artery in rats. Saccular aneurysms grew significantly due to the hemodynamic stress in 4-5 months, and much bigger after the ligation of the contralateral carotid artery which enhanced the hemodynamic stress. There was no PDGF-B expression on the walls of the normal carotid arteries in rats, but it was expressed on the aneurysmal walls and more distinctly with the growth of the saccular aneurysms. However, there was collagen type III expression on the media of the normal carotid artery, but its expression decreased on the aneurysmal walls and further reduced with the growth of the saccular aneurysms. So, PDGF-B may induce the expression of MMP for the degradation of collagen type III on the wall of the saccular aneurysms. This may be one of the important mechanisms on the pathogenesis of the saccular aneurysm.     

大鼠实验性囊状动脉瘤生长塑形模型的建立

目的建立大鼠实验性囊状动脉瘤生长塑形模型。方法通过显微手术方法,破坏大鼠颈动脉分叉部位的内膜和内弹力层诱导囊性动脉瘤,在结扎及未结扎对侧颈总动脉的情况下,观察4-5个月,在长、宽、高三个径线上测量动脉瘤的大小,并行正常动脉和动脉瘤壁的组织学观察。结果通过显微手术方法直接破坏大鼠颈动脉分叉部位的内膜和内弹力层,成功诱导出囊状动脉瘤。经过4-5个月的血流冲击,动脉瘤的长、宽、高均明显增大(P<0.01),并且结扎对侧颈总动脉增加同侧血流冲击,可使动脉瘤在高度上继续增大(P<0.01)。正常动脉壁由内膜、中膜和外膜构成,各层结构保持完整。动脉瘤壁上没有内膜,结构排列紊乱,瘤壁变薄,有炎性细胞浸润。结论囊状动脉瘤在长期血流应力的作用下,逐渐增大生长塑形,提供了一个目前所知的较好的研究囊状动脉瘤生长塑形过程中血管生物学机制的动物模型。     

造影“误判”失去介入治疗机会的颅内动脉瘤

目的对因神经影像判断失去介入治疗机会的动脉瘤,探讨是否能够栓塞治疗。方法 6例脑血管造影发现动脉瘤与分支关系显示不清,瘤颈较宽,瘤体不规则,因此判断不能介入栓塞治疗,改行开颅手术成功夹闭这些动脉瘤。在手术中通过高倍显微镜仔细观察动脉瘤的形态瘤颈宽窄及与周围分支关系,分别予以各种不同角度投照,再与术前CTA及DSA进行对比,寻找这些动脉瘤的特征。结果 6例均发现动脉瘤囊壁与相邻分支紧密相依或者粘连,并且动脉瘤壁对动脉分支压迫使之形成与瘤壁外形相似弧形走形,甚至分支动脉与瘤壁存在"分节段粘连";4例前交通动脉均发现不同程度变异。动脉瘤成功夹闭后,发现形态基本属于"标准"囊状,可以栓塞。结论动脉瘤周围血管正常解剖变异,动脉瘤壁的压迫或者分支动脉不完全粘连,容易出现造影变形,仔细观察或者动脉瘤囊腔内造影可以区别。     

The formation of true saccular aneurysms from diverticula of the cerebral arterial walls

The authors show that aneurysmic diverticula of cerebral vascular walls cam grow in size and to develop, with time, into true saccular aneurysms. Cases of aneurysmic diverticula transformation into aneurysms illustrate dynamic pattern of aneurysmogenesis and formation of this pathology during life. Feasibility of the growth and rupture of the aneurysm in intracranial hemorrhage dictates necessity of follow-up visualizations of cerebral vessels in such patients (contrast angiography, NMR angiography).     

Totally thrombosed giant P2 aneurysm: a case report and review of literature.

The diagnosis and treatment of intracranial saccular giant aneurysms is still difficult despite developments in neuroradiology, neuroanesthesiology and micro-neurosurgery. These aneurysms are usually located on major intracranial arteries and are rarely on distal branches of these arteries. An extra-axial 4 x 5 cm mass lesion in the left mediobasal temporal region was detected on the CT and MRI examinations of a 37 year old male patient who was admitted to our institution with headache and slight right-sided hemiparesis lasting for 2 months. The lesion was avascular on angiography. Surgery proved that the lesion was a totally thrombosed giant aneurysm of the P2 segment of posterior cerebral artery (PCA). The P2 segment was clipped proximal to the aneurysm with pterional-transsylvian approach and the aneurysm was totally excised. Giant aneurysms of the P2 segment are rare and 15 cases have been reported in the literature. This report presents a rarely seen totally thrombosed giant P2 aneurysms and discusses the difficulties in diagnosis and treatment.     

Scanning electron microscopy (S.E.M.) of biopsy specimens of ruptured intracranial saccular aneurysms

Summary Surgical specimens of 4 intracranial saccular aneurysms were studied by scanning electron microscopy. The internal surface of the aneurysms showed crater-like defects and cytoplasmic bridges. In some areas the endothelium was preserved, but its longitudinal convolutions were higher and thicker than those found in unchanged areas. On the damaged endothelial surface there was an increased number of blood cells. The adventitia resembled that of a normal cerebral artery. In conclusion the alterations observed are similar to those found in atherosclerosis and are most likely dut to the high wear and tear provoked by the blood streaming into the aneurysm. The results of this study are in agreement with the findings of a companion transmission electron microscopy study and emphasize the importance of degenerative changes on the development and rupture of intracranial saccular aneurysms.     

Phenotypic modulation of smooth muscle cells in human cerebral aneurysmal walls

We used immunohistochemical methods to analyze the phenotypes of smooth muscle cells (SMCs) in human cerebral arteries and aneurysmal walls. Thirty-two aneurysmal walls were studied; 31 aneurysmal walls were resected at operation and 1 aneurysm was obtained at autopsy. Seven control arteries were obtained at autopsy. Semiserial sections were subjected to immunohistochemical staining with antibodies to α-smooth muscle actin (α-SMA), desmin and smooth muscle myosin heavy chain isoforms: SM1, SM2 and SMemb. In control cerebral arteries, SMCs in the media were strongly immunostained for α-SMA, desmin, SM1 and SM2; immunoreactivity for SMemb was faint or weakly positive. SMCs in both non-ruptured and ruptured aneurysmal walls showed no staining for desmin; the expression of α-SMA was well preserved. Compared with control cerebral arteries, in 4 of 11 non-ruptured aneurysmal walls, the staining intensity of SMCs for SMemb was clearly increased. In ruptured aneurysmal walls, the expression of SM2 was lower than in control cerebral arteries and non-ruptured aneurysmal walls. Our study suggests that the phenotype of SMCs in aneurysmal walls is different from the contractile type in the media of normal cerebral arteries, at least partially changing to the synthetic type in some non-ruptured aneurysms. SMCs in ruptured aneurysmal walls may have lost both phenotypes before rupture. Phenotypic modulation of SMCs in the aneurysmal walls appears to be related to a remodeling of the aneurysmal wall and to a rupture mechanism. Received: 29 October 1999 / Revised, accepted: 7 February 2000     

Matrix metalloproteinases 2 and 9 in human atherosclerotic and non-atherosclerotic cerebral aneurysms

Matrix metalloproteinases 2 and 9 (MMP 2 and -9) have been implicated in the pathogenesis of atherosclerosis and aneurysm formation. The goal of the study was to establish the role of these metalloproteinases in both human atherosclerotic and non-atherosclerotic cerebral aneurysms. Eleven cerebral aneurysms (four atherosclerotic, seven non-atherosclerotic) were immunohistochemically stained for MMP 2 and -9. As controls, atherosclerotic and normal Circle of Willis arteries were similarly immunostained. All specimens were retrieved at autopsy and were paraffin-embedded. In order to evaluate the real MMP 2 and -9 activities, gelatin zymography was also performed in only two available specimens of non-atherosclerotic intracranial aneurysms, because of the relative unavailability of fresh intracranial aneurysm tissue (i.e. reluctance to excise the aneurysm fundus at surgery). Our data establish that MMP 2 and -9 were expressed minimally or not at all in normal Circle of Willis arteries but were strongly expressed in medial smooth muscle cells of atherosclerotic Circle of Willis arteries. In the aneurysm group, both MMP 2 and -9 were strongly expressed in the atherosclerotic aneurysms, but MMP 2 alone was detected in the non-atherosclerotic aneurysms. Zymography revealed a weak enzyme activity correlating to MMP 9 standard recombinant protein. MMP 2 activity was not demonstrated in either specimen. This study shows that the expression of MMP 2 and -9 is associated with atherosclerosis, be it in aneurysmal or non-aneurysmal cerebral vessels but MMP 2 appears to be specifically expressed in aneurysms devoid of atherosclerosis perhaps suggesting a pathogenic role for MMP 2 in the alteration of the extracellular matrix of cerebral arteries during aneurysm formation.